6n8c
From Proteopedia
(Difference between revisions)
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==Structure of the Huntingtin tetramer/dimer mixture determined by paramagnetic NMR== | ==Structure of the Huntingtin tetramer/dimer mixture determined by paramagnetic NMR== | ||
| - | <StructureSection load='6n8c' size='340' side='right' caption='[[6n8c]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''> | + | <StructureSection load='6n8c' size='340' side='right'caption='[[6n8c]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[6n8c]] is a 4 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6N8C OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6N8C FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6n8c]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6N8C OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6N8C FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6n8c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6n8c OCA], [http://pdbe.org/6n8c PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6n8c RCSB], [http://www.ebi.ac.uk/pdbsum/6n8c PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6n8c ProSAT]</span></td></tr> | + | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HTT, HD, IT15 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> |
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6n8c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6n8c OCA], [http://pdbe.org/6n8c PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6n8c RCSB], [http://www.ebi.ac.uk/pdbsum/6n8c PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6n8c ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Disease == | == Disease == | ||
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== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/HD_HUMAN HD_HUMAN]] May play a role in microtubule-mediated transport or vesicle function. | [[http://www.uniprot.org/uniprot/HD_HUMAN HD_HUMAN]] May play a role in microtubule-mediated transport or vesicle function. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The N-terminal region of the huntingtin protein, encoded by exon-1, comprises an amphiphilic domain (htt(NT)), a polyglutamine (Q n ) tract, and a proline-rich sequence. Polyglutamine expansion results in an aggregation-prone protein responsible for Huntington's disease. Here, we study the earliest events involved in oligomerization of a minimalistic construct, htt(NT)Q7, which remains largely monomeric over a sufficiently long period of time to permit detailed quantitative NMR analysis of the kinetics and structure of sparsely populated [Formula: see text] oligomeric states, yet still eventually forms fibrils. Global fitting of concentration-dependent relaxation dispersion, transverse relaxation in the rotating frame, and exchange-induced chemical shift data reveals a bifurcated assembly mechanism in which the NMR observable monomeric species either self-associates to form a productive dimer (tauex approximately 30 mus, K diss approximately 0.1 M) that goes on to form a tetramer ([Formula: see text] mus; K diss approximately 22 muM), or exchanges with a "nonproductive" dimer that does not oligomerize further (tauex approximately 400 mus; K diss approximately 0.3 M). The excited state backbone chemical shifts are indicative of a contiguous helix (residues 3-17) in the productive dimer/tetramer, with only partial helical character in the nonproductive dimer. A structural model of the productive dimer/tetramer was obtained by simulated annealing driven by intermolecular paramagnetic relaxation enhancement data. The tetramer comprises a D 2 symmetric dimer of dimers with largely hydrophobic packing between the helical subunits. The structural model, validated by EPR distance measurements, illuminates the role of the htt(NT) domain in the earliest stages of prenucleation and oligomerization, before fibril formation. | ||
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| + | Probing initial transient oligomerization events facilitating Huntingtin fibril nucleation at atomic resolution by relaxation-based NMR.,Kotler SA, Tugarinov V, Schmidt T, Ceccon A, Libich DS, Ghirlando R, Schwieters CD, Clore GM Proc Natl Acad Sci U S A. 2019 Feb 26;116(9):3562-3571. doi:, 10.1073/pnas.1821216116. Epub 2019 Feb 11. PMID:30808748<ref>PMID:30808748</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6n8c" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Human]] | ||
| + | [[Category: Large Structures]] | ||
[[Category: Ceccon, A]] | [[Category: Ceccon, A]] | ||
[[Category: Clore, G M]] | [[Category: Clore, G M]] | ||
Revision as of 12:47, 13 March 2019
Structure of the Huntingtin tetramer/dimer mixture determined by paramagnetic NMR
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