This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

4aix

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Revision as of 19:12, 10 December 2016

Crystallographic structure of an amyloidogenic variant, 3rC34Y, of the germinal line lambda 3

Structural highlights

4aix is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	4aiz, 4aj0
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Publication Abstract from PubMed

Light chain amyloidosis (AL) is a disease which affects vital organs by the fibrillar aggregation of monoclonal light chains. lambda3r germ line is significantly implicated in this disease. In this work, we contrasted the thermodynamic stability and aggregation propensity of 3mJL2 (non amyloidogenic) and 3rJL2 (amyloidogenic) lambda3 germ lines. Due to an inherent limitation (extremely low expression), Cys at position 34 of the 3r germ-line, was replaced by Tyr reaching a good expression yield. A second substitution (W91A), was introduced in 3r in order to obtain a better template to incorporate additional mutations. Although the single mutant (C34Y) was not fibrillogenic, the second mutation located at CDR3 (W91A), induced fibrillogenesis. We propose, for the first time, that CDR3 (position 91) affects the stability and fiber formation of human lambda3r light chains. Using the double mutant (3rJL2/YA) as template, other variants were constructed in order to evaluate the importance of those substitutions into the stability and aggregation propensity of lambda3 light chains. A change in position 7 (P7D), boosted 3rJL2/YA fibrillogenic properties. Modification of position 48 (I48M) partially reverted 3rJL2/YA fibril aggregation. Finally, changes at positions 8 (P8S) or 40 (P40S) completely reverted fibril formation. These results confirm the influential roles of N-terminal region (positions 7 and 8) and the loop 40-60 (positions 40 and 48) on (AL) amyloidosis. X-ray crystallography revealed that the three-dimensional topology of the single and double lambda3r mutants was not significantly altered. This mutagenic approach, helped to identify key regions implicated in lambda3 (AL) amyloidosis.

Site-directed Mutagenesis Reveals Regions Implicated in the Stability and Fiber Formation of Human lambda3r Light Chains.,Villalba MI, Canul-Tec JC, Luna-Martinez OD, Sanchez-Alcala R, Olamendi-Portugal T, Rudino-Pinera E, Rojas S, Sanchez-Lopez R, Fernandez-Velasco DA, Becerril B J Biol Chem. 2014 Dec 11. pii: jbc.M114.629550. PMID:25505244^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Villalba MI, Canul-Tec JC, Luna-Martinez OD, Sanchez-Alcala R, Olamendi-Portugal T, Rudino-Pinera E, Rojas S, Sanchez-Lopez R, Fernandez-Velasco DA, Becerril B. Site-directed Mutagenesis Reveals Regions Implicated in the Stability and Fiber Formation of Human lambda3r Light Chains. J Biol Chem. 2014 Dec 11. pii: jbc.M114.629550. PMID:25505244 doi:http://dx.doi.org/10.1074/jbc.M114.629550

1 Structural highlights
2 Publication Abstract from PubMed
3 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4aix"

@@ Line 1: / Line 1: @@
 ==Crystallographic structure of an amyloidogenic variant, 3rC34Y, of the germinal line lambda 3==
 <StructureSection load='4aix' size='340' side='right' caption='[[4aix]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
@@ Line 4: / Line 5: @@
 <table><tr><td colspan='2'>[[4aix]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4AIX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4AIX FirstGlance]. <br>
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4aiz|4aiz]], [[4aj0|4aj0]]</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=4aix FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4aix OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4aix RCSB], [http://www.ebi.ac.uk/pdbsum/4aix PDBsum]</span></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=4aix FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4aix OCA], [http://pdbe.org/4aix PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4aix RCSB], [http://www.ebi.ac.uk/pdbsum/4aix PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4aix ProSAT]</span></td></tr>
 </table>
 <div style="background-color:#fffaf0;">
@@ Line 14: / Line 15: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4aix" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

4aix

From Proteopedia

Revision as of 19:12, 10 December 2016

Crystallographic structure of an amyloidogenic variant, 3rC34Y, of the germinal line lambda 3

Structural highlights

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox