Molecular playground/beta 2 microglobulin - Revision history

http://52.214.119.220/wiki/index.php?action=history&feed=atom&title=Molecular_playground%2Fbeta_2_microglobulin Molecular playground/beta 2 microglobulin - Revision history 2026-04-04T02:51:07Z Revision history for this page on the wiki MediaWiki 1.11.2 http://52.214.119.220/wiki/index.php?title=Molecular_playground/beta_2_microglobulin&diff=2102899&oldid=prev Tyler Marcinko at 20:07, 11 December 2014 2014-12-11T20:07:28Z

<p></p> <table style="background-color: white; color:black;"> <col class='diff-marker' /> <col class='diff-content' /> <col class='diff-marker' /> <col class='diff-content' /> <tr> <td colspan='2' style="background-color: white; color:black;">←Older revision</td> <td colspan='2' style="background-color: white; color:black;">Revision as of 20:07, 11 December 2014</td> </tr> <tr><td colspan="2" class="diff-lineno">Line 16:</td> <td colspan="2" class="diff-lineno">Line 16:</td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>One hypothesis has emerged that the cis-trans isomerization of Pro32 is critical to the aggregation process. The <scene name='38/389965/141211_p32a/3'>P32A</scene> mutant has proved to be useful in this regard. With the Ala in the trans position, copper binding is enhanced 10,000 fold and has similar oligomerization kinetics to that of wild type-β2m. However, the structural effects of the mutation lead to an alternative dimer structure <ref>3</ref>. Seen here as a tetramer, it appears that the oligomer adopts a intermolecular β-sheet structure which is a hallmark of amyloids.</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>One hypothesis has emerged that the cis-trans isomerization of Pro32 is critical to the aggregation process. The <scene name='38/389965/141211_p32a/3'>P32A</scene> mutant has proved to be useful in this regard. With the Ala in the trans position, copper binding is enhanced 10,000 fold and has similar oligomerization kinetics to that of wild type-β2m. However, the structural effects of the mutation lead to an alternative dimer structure <ref>3</ref>. Seen here as a tetramer, it appears that the oligomer adopts a intermolecular β-sheet structure which is a hallmark of amyloids.</div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'>-</td><td style="background: #ffa; color:black; font-size: smaller;"><div>The critical residue for copper binding, H31, has also been investigated. By mutating His31 to a Tyr, the positive charge is neutralized and the local environment <del style="color: red; font-weight: bold; text-decoration: none;">should be </del>minimally perturbed. Indeed, the H31Y mutant has increased stability relative to wild type and has reduced copper binding characteristics <ref>4</ref>.</div></td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div>The critical residue for copper binding, H31, has also been investigated. By mutating His31 to a Tyr, the positive charge is neutralized and the local environment <ins style="color: red; font-weight: bold; text-decoration: none;">is </ins>minimally perturbed. Indeed, the H31Y mutant has increased stability relative to wild type and has reduced copper binding characteristics <ref>4</ref>.</div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>==Additional Resources==</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>==Additional Resources==</div></td></tr> </table>

Tyler Marcinko http://52.214.119.220/wiki/index.php?title=Molecular_playground/beta_2_microglobulin&diff=2102898&oldid=prev Tyler Marcinko at 20:03, 11 December 2014 2014-12-11T20:03:06Z

<p></p> <table style="background-color: white; color:black;"> <col class='diff-marker' /> <col class='diff-content' /> <col class='diff-marker' /> <col class='diff-content' /> <tr> <td colspan='2' style="background-color: white; color:black;">←Older revision</td> <td colspan='2' style="background-color: white; color:black;">Revision as of 20:03, 11 December 2014</td> </tr> <tr><td colspan="2" class="diff-lineno">Line 12:</td> <td colspan="2" class="diff-lineno">Line 12:</td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>== Elucidating Early Aggregation Events ==</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>== Elucidating Early Aggregation Events ==</div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'>-</td><td style="background: #ffa; color:black; font-size: smaller;"><div>There have been several mutants of β2m generated that have been essential in defining some of the early molecular events that ultimately lead to destabilization and ultimately oligomerization. The <scene name='38/389965/<del style="color: red; font-weight: bold; text-decoration: none;">H13f_hexamer</del>/1'>H13F</scene> variant of β2m has permitted the structure of the putative hexamer to be solved. However, this mutation apparently precludes the formation of long amyloid fibrils and instead progress to off-pathway oligomers <ref>2</ref>.</div></td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div>There have been several mutants of β2m generated that have been essential in defining some of the early molecular events that ultimately lead to destabilization and ultimately oligomerization. The <scene name='38/389965/<ins style="color: red; font-weight: bold; text-decoration: none;">141211_h13f</ins>/1'>H13F</scene> variant of β2m has permitted the structure of the putative hexamer to be solved. However, this mutation apparently precludes the formation of long amyloid fibrils and instead progress to off-pathway oligomers <ref>2</ref>.</div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>One hypothesis has emerged that the cis-trans isomerization of Pro32 is critical to the aggregation process. The <scene name='38/389965/141211_p32a/3'>P32A</scene> mutant has proved to be useful in this regard. With the Ala in the trans position, copper binding is enhanced 10,000 fold and has similar oligomerization kinetics to that of wild type-β2m. However, the structural effects of the mutation lead to an alternative dimer structure <ref>3</ref>. Seen here as a tetramer, it appears that the oligomer adopts a intermolecular β-sheet structure which is a hallmark of amyloids.</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>One hypothesis has emerged that the cis-trans isomerization of Pro32 is critical to the aggregation process. The <scene name='38/389965/141211_p32a/3'>P32A</scene> mutant has proved to be useful in this regard. With the Ala in the trans position, copper binding is enhanced 10,000 fold and has similar oligomerization kinetics to that of wild type-β2m. However, the structural effects of the mutation lead to an alternative dimer structure <ref>3</ref>. Seen here as a tetramer, it appears that the oligomer adopts a intermolecular β-sheet structure which is a hallmark of amyloids.</div></td></tr> </table>

Tyler Marcinko http://52.214.119.220/wiki/index.php?title=Molecular_playground/beta_2_microglobulin&diff=2102897&oldid=prev Tyler Marcinko at 19:56, 11 December 2014 2014-12-11T19:56:09Z

<p></p> <table style="background-color: white; color:black;"> <col class='diff-marker' /> <col class='diff-content' /> <col class='diff-marker' /> <col class='diff-content' /> <tr> <td colspan='2' style="background-color: white; color:black;">←Older revision</td> <td colspan='2' style="background-color: white; color:black;">Revision as of 19:56, 11 December 2014</td> </tr> <tr><td colspan="2" class="diff-lineno">Line 14:</td> <td colspan="2" class="diff-lineno">Line 14:</td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>There have been several mutants of β2m generated that have been essential in defining some of the early molecular events that ultimately lead to destabilization and ultimately oligomerization. The <scene name='38/389965/H13f_hexamer/1'>H13F</scene> variant of β2m has permitted the structure of the putative hexamer to be solved. However, this mutation apparently precludes the formation of long amyloid fibrils and instead progress to off-pathway oligomers <ref>2</ref>.</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>There have been several mutants of β2m generated that have been essential in defining some of the early molecular events that ultimately lead to destabilization and ultimately oligomerization. The <scene name='38/389965/H13f_hexamer/1'>H13F</scene> variant of β2m has permitted the structure of the putative hexamer to be solved. However, this mutation apparently precludes the formation of long amyloid fibrils and instead progress to off-pathway oligomers <ref>2</ref>.</div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'>-</td><td style="background: #ffa; color:black; font-size: smaller;"><div>One hypothesis has emerged that the cis-trans isomerization of Pro32 is critical to the aggregation process. The <scene name='38/389965/141211_p32a/<del style="color: red; font-weight: bold; text-decoration: none;">2</del>'>P32A</scene> mutant has proved to be useful in this regard. With the Ala in the trans position, copper binding is enhanced 10,000 fold and has similar oligomerization kinetics to that of wild type-β2m. However, the structural effects of the mutation lead to an alternative dimer structure <ref>3</ref>. Seen here as a tetramer, it appears that the oligomer adopts a intermolecular β-sheet structure which is a hallmark of amyloids.</div></td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div>One hypothesis has emerged that the cis-trans isomerization of Pro32 is critical to the aggregation process. The <scene name='38/389965/141211_p32a/<ins style="color: red; font-weight: bold; text-decoration: none;">3</ins>'>P32A</scene> mutant has proved to be useful in this regard. With the Ala in the trans position, copper binding is enhanced 10,000 fold and has similar oligomerization kinetics to that of wild type-β2m. However, the structural effects of the mutation lead to an alternative dimer structure <ref>3</ref>. Seen here as a tetramer, it appears that the oligomer adopts a intermolecular β-sheet structure which is a hallmark of amyloids.</div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>The critical residue for copper binding, H31, has also been investigated. By mutating His31 to a Tyr, the positive charge is neutralized and the local environment should be minimally perturbed. Indeed, the H31Y mutant has increased stability relative to wild type and has reduced copper binding characteristics <ref>4</ref>.</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>The critical residue for copper binding, H31, has also been investigated. By mutating His31 to a Tyr, the positive charge is neutralized and the local environment should be minimally perturbed. Indeed, the H31Y mutant has increased stability relative to wild type and has reduced copper binding characteristics <ref>4</ref>.</div></td></tr> </table>

Tyler Marcinko http://52.214.119.220/wiki/index.php?title=Molecular_playground/beta_2_microglobulin&diff=2102896&oldid=prev Tyler Marcinko at 19:49, 11 December 2014 2014-12-11T19:49:16Z

<p></p> <table style="background-color: white; color:black;"> <col class='diff-marker' /> <col class='diff-content' /> <col class='diff-marker' /> <col class='diff-content' /> <tr> <td colspan='2' style="background-color: white; color:black;">←Older revision</td> <td colspan='2' style="background-color: white; color:black;">Revision as of 19:49, 11 December 2014</td> </tr> <tr><td colspan="2" class="diff-lineno">Line 14:</td> <td colspan="2" class="diff-lineno">Line 14:</td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>There have been several mutants of β2m generated that have been essential in defining some of the early molecular events that ultimately lead to destabilization and ultimately oligomerization. The <scene name='38/389965/H13f_hexamer/1'>H13F</scene> variant of β2m has permitted the structure of the putative hexamer to be solved. However, this mutation apparently precludes the formation of long amyloid fibrils and instead progress to off-pathway oligomers <ref>2</ref>.</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>There have been several mutants of β2m generated that have been essential in defining some of the early molecular events that ultimately lead to destabilization and ultimately oligomerization. The <scene name='38/389965/H13f_hexamer/1'>H13F</scene> variant of β2m has permitted the structure of the putative hexamer to be solved. However, this mutation apparently precludes the formation of long amyloid fibrils and instead progress to off-pathway oligomers <ref>2</ref>.</div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'>-</td><td style="background: #ffa; color:black; font-size: smaller;"><div>One hypothesis has emerged that the cis-trans isomerization of Pro32 is critical to the aggregation process. The <scene name='38/389965/141211_p32a/<del style="color: red; font-weight: bold; text-decoration: none;">1</del>'>P32A</scene> mutant has proved to be useful in this regard. With the Ala in the trans position, copper binding is enhanced 10,000 fold and has similar oligomerization kinetics to that of wild type-β2m. However, the structural effects of the mutation lead to an alternative dimer structure <ref>3</ref>. Seen here as a tetramer, it appears that the oligomer adopts a intermolecular β-sheet structure which is a hallmark of amyloids.</div></td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div>One hypothesis has emerged that the cis-trans isomerization of Pro32 is critical to the aggregation process. The <scene name='38/389965/141211_p32a/<ins style="color: red; font-weight: bold; text-decoration: none;">2</ins>'>P32A</scene> mutant has proved to be useful in this regard. With the Ala in the trans position, copper binding is enhanced 10,000 fold and has similar oligomerization kinetics to that of wild type-β2m. However, the structural effects of the mutation lead to an alternative dimer structure <ref>3</ref>. Seen here as a tetramer, it appears that the oligomer adopts a intermolecular β-sheet structure which is a hallmark of amyloids.</div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>The critical residue for copper binding, H31, has also been investigated. By mutating His31 to a Tyr, the positive charge is neutralized and the local environment should be minimally perturbed. Indeed, the H31Y mutant has increased stability relative to wild type and has reduced copper binding characteristics <ref>4</ref>.</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>The critical residue for copper binding, H31, has also been investigated. By mutating His31 to a Tyr, the positive charge is neutralized and the local environment should be minimally perturbed. Indeed, the H31Y mutant has increased stability relative to wild type and has reduced copper binding characteristics <ref>4</ref>.</div></td></tr> </table>

Tyler Marcinko http://52.214.119.220/wiki/index.php?title=Molecular_playground/beta_2_microglobulin&diff=2102895&oldid=prev Tyler Marcinko at 19:44, 11 December 2014 2014-12-11T19:44:14Z

<p></p> <table style="background-color: white; color:black;"> <col class='diff-marker' /> <col class='diff-content' /> <col class='diff-marker' /> <col class='diff-content' /> <tr> <td colspan='2' style="background-color: white; color:black;">←Older revision</td> <td colspan='2' style="background-color: white; color:black;">Revision as of 19:44, 11 December 2014</td> </tr> <tr><td colspan="2" class="diff-lineno">Line 14:</td> <td colspan="2" class="diff-lineno">Line 14:</td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>There have been several mutants of β2m generated that have been essential in defining some of the early molecular events that ultimately lead to destabilization and ultimately oligomerization. The <scene name='38/389965/H13f_hexamer/1'>H13F</scene> variant of β2m has permitted the structure of the putative hexamer to be solved. However, this mutation apparently precludes the formation of long amyloid fibrils and instead progress to off-pathway oligomers <ref>2</ref>.</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>There have been several mutants of β2m generated that have been essential in defining some of the early molecular events that ultimately lead to destabilization and ultimately oligomerization. The <scene name='38/389965/H13f_hexamer/1'>H13F</scene> variant of β2m has permitted the structure of the putative hexamer to be solved. However, this mutation apparently precludes the formation of long amyloid fibrils and instead progress to off-pathway oligomers <ref>2</ref>.</div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'>-</td><td style="background: #ffa; color:black; font-size: smaller;"><div>One hypothesis has emerged that the cis-trans isomerization of Pro32 is critical to the aggregation process. The <scene name='38/389965/<del style="color: red; font-weight: bold; text-decoration: none;">P32a_alt_dimer</del>/<del style="color: red; font-weight: bold; text-decoration: none;">3</del>'>P32A</scene> mutant has proved to be useful in this regard. With the Ala in the trans position, copper binding is enhanced 10,000 fold and has similar oligomerization kinetics to that of wild type-β2m. However, the structural effects of the mutation lead to an alternative dimer structure <ref>3</ref>. Seen here as a tetramer, it appears that the oligomer adopts a intermolecular β-sheet structure which is a hallmark of amyloids.</div></td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div>One hypothesis has emerged that the cis-trans isomerization of Pro32 is critical to the aggregation process. The <scene name='38/389965/<ins style="color: red; font-weight: bold; text-decoration: none;">141211_p32a</ins>/<ins style="color: red; font-weight: bold; text-decoration: none;">1</ins>'>P32A</scene> mutant has proved to be useful in this regard. With the Ala in the trans position, copper binding is enhanced 10,000 fold and has similar oligomerization kinetics to that of wild type-β2m. However, the structural effects of the mutation lead to an alternative dimer structure <ref>3</ref>. Seen here as a tetramer, it appears that the oligomer adopts a intermolecular β-sheet structure which is a hallmark of amyloids.</div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>The critical residue for copper binding, H31, has also been investigated. By mutating His31 to a Tyr, the positive charge is neutralized and the local environment should be minimally perturbed. Indeed, the H31Y mutant has increased stability relative to wild type and has reduced copper binding characteristics <ref>4</ref>.</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>The critical residue for copper binding, H31, has also been investigated. By mutating His31 to a Tyr, the positive charge is neutralized and the local environment should be minimally perturbed. Indeed, the H31Y mutant has increased stability relative to wild type and has reduced copper binding characteristics <ref>4</ref>.</div></td></tr> </table>

Tyler Marcinko http://52.214.119.220/wiki/index.php?title=Molecular_playground/beta_2_microglobulin&diff=2102894&oldid=prev Tyler Marcinko at 19:37, 11 December 2014 2014-12-11T19:37:48Z

<p></p> <table style="background-color: white; color:black;"> <col class='diff-marker' /> <col class='diff-content' /> <col class='diff-marker' /> <col class='diff-content' /> <tr> <td colspan='2' style="background-color: white; color:black;">←Older revision</td> <td colspan='2' style="background-color: white; color:black;">Revision as of 19:37, 11 December 2014</td> </tr> <tr><td colspan="2" class="diff-lineno">Line 14:</td> <td colspan="2" class="diff-lineno">Line 14:</td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>There have been several mutants of β2m generated that have been essential in defining some of the early molecular events that ultimately lead to destabilization and ultimately oligomerization. The <scene name='38/389965/H13f_hexamer/1'>H13F</scene> variant of β2m has permitted the structure of the putative hexamer to be solved. However, this mutation apparently precludes the formation of long amyloid fibrils and instead progress to off-pathway oligomers <ref>2</ref>.</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>There have been several mutants of β2m generated that have been essential in defining some of the early molecular events that ultimately lead to destabilization and ultimately oligomerization. The <scene name='38/389965/H13f_hexamer/1'>H13F</scene> variant of β2m has permitted the structure of the putative hexamer to be solved. However, this mutation apparently precludes the formation of long amyloid fibrils and instead progress to off-pathway oligomers <ref>2</ref>.</div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'>-</td><td style="background: #ffa; color:black; font-size: smaller;"><div>One hypothesis has emerged that the cis-trans isomerization of Pro32 is critical to the aggregation process. The <del style="color: red; font-weight: bold; text-decoration: none;">dimer of </del><scene name='38/389965/P32a_alt_dimer/3'>P32A</scene> has proved to be useful in this regard. With the Ala in the trans position, copper binding is enhanced 10,000 fold and has similar oligomerization kinetics to that of wild type-β2m. However, the structural effects of the mutation lead to an alternative dimer structure <ref>3</ref>.</div></td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div>One hypothesis has emerged that the cis-trans isomerization of Pro32 is critical to the aggregation process. The <scene name='38/389965/P32a_alt_dimer/3'>P32A</scene> <ins style="color: red; font-weight: bold; text-decoration: none;">mutant </ins>has proved to be useful in this regard. With the Ala in the trans position, copper binding is enhanced 10,000 fold and has similar oligomerization kinetics to that of wild type-β2m. However, the structural effects of the mutation lead to an alternative dimer structure <ref>3</ref><ins style="color: red; font-weight: bold; text-decoration: none;">. Seen here as a tetramer, it appears that the oligomer adopts a intermolecular β-sheet structure which is a hallmark of amyloids</ins>.</div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>The critical residue for copper binding, H31, has also been investigated. By mutating His31 to a Tyr, the positive charge is neutralized and the local environment should be minimally perturbed. Indeed, the H31Y mutant has increased stability relative to wild type and has reduced copper binding characteristics <ref>4</ref>.</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>The critical residue for copper binding, H31, has also been investigated. By mutating His31 to a Tyr, the positive charge is neutralized and the local environment should be minimally perturbed. Indeed, the H31Y mutant has increased stability relative to wild type and has reduced copper binding characteristics <ref>4</ref>.</div></td></tr> </table>

Tyler Marcinko http://52.214.119.220/wiki/index.php?title=Molecular_playground/beta_2_microglobulin&diff=2102893&oldid=prev Tyler Marcinko at 19:26, 11 December 2014 2014-12-11T19:26:46Z

<p></p> <table style="background-color: white; color:black;"> <col class='diff-marker' /> <col class='diff-content' /> <col class='diff-marker' /> <col class='diff-content' /> <tr> <td colspan='2' style="background-color: white; color:black;">←Older revision</td> <td colspan='2' style="background-color: white; color:black;">Revision as of 19:26, 11 December 2014</td> </tr> <tr><td colspan="2" class="diff-lineno">Line 14:</td> <td colspan="2" class="diff-lineno">Line 14:</td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>There have been several mutants of β2m generated that have been essential in defining some of the early molecular events that ultimately lead to destabilization and ultimately oligomerization. The <scene name='38/389965/H13f_hexamer/1'>H13F</scene> variant of β2m has permitted the structure of the putative hexamer to be solved. However, this mutation apparently precludes the formation of long amyloid fibrils and instead progress to off-pathway oligomers <ref>2</ref>.</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>There have been several mutants of β2m generated that have been essential in defining some of the early molecular events that ultimately lead to destabilization and ultimately oligomerization. The <scene name='38/389965/H13f_hexamer/1'>H13F</scene> variant of β2m has permitted the structure of the putative hexamer to be solved. However, this mutation apparently precludes the formation of long amyloid fibrils and instead progress to off-pathway oligomers <ref>2</ref>.</div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'>-</td><td style="background: #ffa; color:black; font-size: smaller;"><div>One hypothesis has emerged that the cis-trans isomerization of Pro32 is critical to the aggregation process. The dimer of <scene name='38/389965/<del style="color: red; font-weight: bold; text-decoration: none;">P32a_test</del>/<del style="color: red; font-weight: bold; text-decoration: none;">1</del>'>P32A</scene> has proved to be useful in this regard. With the Ala in the trans position, copper binding is enhanced 10,000 fold and has similar oligomerization kinetics to that of wild type-β2m. However, the structural effects of the mutation lead to an alternative dimer structure <ref>3</ref>.</div></td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div>One hypothesis has emerged that the cis-trans isomerization of Pro32 is critical to the aggregation process. The dimer of <scene name='38/389965/<ins style="color: red; font-weight: bold; text-decoration: none;">P32a_alt_dimer</ins>/<ins style="color: red; font-weight: bold; text-decoration: none;">3</ins>'>P32A</scene> has proved to be useful in this regard. With the Ala in the trans position, copper binding is enhanced 10,000 fold and has similar oligomerization kinetics to that of wild type-β2m. However, the structural effects of the mutation lead to an alternative dimer structure <ref>3</ref>.</div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>The critical residue for copper binding, H31, has also been investigated. By mutating His31 to a Tyr, the positive charge is neutralized and the local environment should be minimally perturbed. Indeed, the H31Y mutant has increased stability relative to wild type and has reduced copper binding characteristics <ref>4</ref>.</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>The critical residue for copper binding, H31, has also been investigated. By mutating His31 to a Tyr, the positive charge is neutralized and the local environment should be minimally perturbed. Indeed, the H31Y mutant has increased stability relative to wild type and has reduced copper binding characteristics <ref>4</ref>.</div></td></tr> </table>

Tyler Marcinko http://52.214.119.220/wiki/index.php?title=Molecular_playground/beta_2_microglobulin&diff=2102892&oldid=prev Tyler Marcinko at 19:18, 11 December 2014 2014-12-11T19:18:54Z

<p></p> <table style="background-color: white; color:black;"> <col class='diff-marker' /> <col class='diff-content' /> <col class='diff-marker' /> <col class='diff-content' /> <tr> <td colspan='2' style="background-color: white; color:black;">←Older revision</td> <td colspan='2' style="background-color: white; color:black;">Revision as of 19:18, 11 December 2014</td> </tr> <tr><td colspan="2" class="diff-lineno">Line 8:</td> <td colspan="2" class="diff-lineno">Line 8:</td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>There are several processes that can cause β2m to aggregate and ultimately form amyloid fibrils. This includes exposure to low pH, cleavage of the first residues from the N-terminus, incubation with collagen, and exposure to elemental copper. In the copper-catalyzed pathway, the process begins with the formation of a homodimer. His31 is a critical residue for cation binding. Dimer formation is initiated when copper binds near the <scene name='User:Nick_Borotto/Sandbox_1/Metal_coordination_site/4'>N-terminus</scene>. Copper binding causes structural changes throughout the protein creating two new planes. These planes interact in an antiparallel fashion which forms the basis of the non-covalent <scene name='User:Nick_Borotto/Sandbox_1/Proposed_dimer_structure/3'>dimer</scene>.</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>There are several processes that can cause β2m to aggregate and ultimately form amyloid fibrils. This includes exposure to low pH, cleavage of the first residues from the N-terminus, incubation with collagen, and exposure to elemental copper. In the copper-catalyzed pathway, the process begins with the formation of a homodimer. His31 is a critical residue for cation binding. Dimer formation is initiated when copper binds near the <scene name='User:Nick_Borotto/Sandbox_1/Metal_coordination_site/4'>N-terminus</scene>. Copper binding causes structural changes throughout the protein creating two new planes. These planes interact in an antiparallel fashion which forms the basis of the non-covalent <scene name='User:Nick_Borotto/Sandbox_1/Proposed_dimer_structure/3'>dimer</scene>.</div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'>-</td><td style="background: #ffa; color:black; font-size: smaller;"><div>Soluble <del style="color: red; font-weight: bold; text-decoration: none;">oligomers </del>then undergo higher order assembly steps to form larger structures. Evidence for the tetramer and hexamer have been measured using a variety of different analytical methods. Formation of these species eventually leads to the formation of proto-fibril nuclei which serve to then elongate into mature insoluble fibrils.</div></td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div>Soluble <ins style="color: red; font-weight: bold; text-decoration: none;">dimers </ins>then undergo higher order assembly steps to form larger structures. Evidence for the tetramer and hexamer have been measured using a variety of different analytical methods. Formation of these species eventually leads to the formation of proto-fibril nuclei which serve to then elongate into mature insoluble fibrils.</div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>== Elucidating Early Aggregation Events ==</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>== Elucidating Early Aggregation Events ==</div></td></tr> </table>

Tyler Marcinko http://52.214.119.220/wiki/index.php?title=Molecular_playground/beta_2_microglobulin&diff=2102891&oldid=prev Tyler Marcinko at 14:12, 11 December 2014 2014-12-11T14:12:14Z

<p></p> <table style="background-color: white; color:black;"> <col class='diff-marker' /> <col class='diff-content' /> <col class='diff-marker' /> <col class='diff-content' /> <tr> <td colspan='2' style="background-color: white; color:black;">←Older revision</td> <td colspan='2' style="background-color: white; color:black;">Revision as of 14:12, 11 December 2014</td> </tr> <tr><td colspan="2" class="diff-lineno">Line 12:</td> <td colspan="2" class="diff-lineno">Line 12:</td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>== Elucidating Early Aggregation Events ==</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>== Elucidating Early Aggregation Events ==</div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'>-</td><td style="background: #ffa; color:black; font-size: smaller;"><div>There have been several mutants of β2m generated that have been essential in defining some of the early molecular events that ultimately lead to <del style="color: red; font-weight: bold; text-decoration: none;">amyloidosis</del>. The <scene name='38/389965/H13f_hexamer/1'>H13F</scene> variant of β2m has permitted the structure of the putative hexamer to be solved. However, this mutation apparently precludes the formation of long amyloid fibrils and instead progress to off-pathway oligomers <ref>2</ref>.</div></td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div>There have been several mutants of β2m generated that have been essential in defining some of the early molecular events that ultimately lead to <ins style="color: red; font-weight: bold; text-decoration: none;">destabilization and ultimately oligomerization</ins>. The <scene name='38/389965/H13f_hexamer/1'>H13F</scene> variant of β2m has permitted the structure of the putative hexamer to be solved. However, this mutation apparently precludes the formation of long amyloid fibrils and instead progress to off-pathway oligomers <ref>2</ref>.</div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>One hypothesis has emerged that the cis-trans isomerization of Pro32 is critical to the aggregation process. The dimer of <scene name='38/389965/P32a_test/1'>P32A</scene> has proved to be useful in this regard. With the Ala in the trans position, copper binding is enhanced 10,000 fold and has similar oligomerization kinetics to that of wild type-β2m. However, the structural effects of the mutation lead to an alternative dimer structure <ref>3</ref>.</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>One hypothesis has emerged that the cis-trans isomerization of Pro32 is critical to the aggregation process. The dimer of <scene name='38/389965/P32a_test/1'>P32A</scene> has proved to be useful in this regard. With the Ala in the trans position, copper binding is enhanced 10,000 fold and has similar oligomerization kinetics to that of wild type-β2m. However, the structural effects of the mutation lead to an alternative dimer structure <ref>3</ref>.</div></td></tr> </table>

Tyler Marcinko http://52.214.119.220/wiki/index.php?title=Molecular_playground/beta_2_microglobulin&diff=2102795&oldid=prev Tyler Marcinko at 21:23, 10 December 2014 2014-12-10T21:23:50Z

<p></p> <table style="background-color: white; color:black;"> <col class='diff-marker' /> <col class='diff-content' /> <col class='diff-marker' /> <col class='diff-content' /> <tr> <td colspan='2' style="background-color: white; color:black;">←Older revision</td> <td colspan='2' style="background-color: white; color:black;">Revision as of 21:23, 10 December 2014</td> </tr> <tr><td colspan="2" class="diff-lineno">Line 14:</td> <td colspan="2" class="diff-lineno">Line 14:</td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>There have been several mutants of β2m generated that have been essential in defining some of the early molecular events that ultimately lead to amyloidosis. The <scene name='38/389965/H13f_hexamer/1'>H13F</scene> variant of β2m has permitted the structure of the putative hexamer to be solved. However, this mutation apparently precludes the formation of long amyloid fibrils and instead progress to off-pathway oligomers <ref>2</ref>.</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>There have been several mutants of β2m generated that have been essential in defining some of the early molecular events that ultimately lead to amyloidosis. The <scene name='38/389965/H13f_hexamer/1'>H13F</scene> variant of β2m has permitted the structure of the putative hexamer to be solved. However, this mutation apparently precludes the formation of long amyloid fibrils and instead progress to off-pathway oligomers <ref>2</ref>.</div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'>-</td><td style="background: #ffa; color:black; font-size: smaller;"><div>One hypothesis has emerged that the cis-trans isomerization of Pro32 is critical to the aggregation process. The dimer of <scene name='38/389965/<del style="color: red; font-weight: bold; text-decoration: none;">P32a_tetramer2</del>/1'>P32A</scene> has proved to be useful in this regard. With the Ala in the trans position, copper binding is enhanced 10,000 fold and has similar oligomerization kinetics to that of wild type-β2m. However, the structural effects of the mutation lead to an alternative dimer structure <ref>3</ref>.</div></td><td class='diff-marker'>+</td><td style="background: #cfc; color:black; font-size: smaller;"><div>One hypothesis has emerged that the cis-trans isomerization of Pro32 is critical to the aggregation process. The dimer of <scene name='38/389965/<ins style="color: red; font-weight: bold; text-decoration: none;">P32a_test</ins>/1'>P32A</scene> has proved to be useful in this regard. With the Ala in the trans position, copper binding is enhanced 10,000 fold and has similar oligomerization kinetics to that of wild type-β2m. However, the structural effects of the mutation lead to an alternative dimer structure <ref>3</ref>.</div></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"></td></tr> <tr><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>The critical residue for copper binding, H31, has also been investigated. By mutating His31 to a Tyr, the positive charge is neutralized and the local environment should be minimally perturbed. Indeed, the H31Y mutant has increased stability relative to wild type and has reduced copper binding characteristics <ref>4</ref>.</div></td><td class='diff-marker'> </td><td style="background: #eee; color:black; font-size: smaller;"><div>The critical residue for copper binding, H31, has also been investigated. By mutating His31 to a Tyr, the positive charge is neutralized and the local environment should be minimally perturbed. Indeed, the H31Y mutant has increased stability relative to wild type and has reduced copper binding characteristics <ref>4</ref>.</div></td></tr> </table>

Tyler Marcinko