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5ir3

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Revision as of 10:02, 22 November 2017

Crystal structure of the recombinant highest fibrillogenic natural mutant (obtained from patient AR) derived from lambda 6 light chain variable domain

Structural highlights

5ir3 is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	3bdx, 3b5g, 5c9k, 2w0k
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[LV657_HUMAN] V region of the variable domain of immunoglobulin light chains that participates in the antigen recognition (PubMed:24600447). Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral immunity, the membrane-bound immunoglobulins serve as receptors which, upon binding of a specific antigen, trigger the clonal expansion and differentiation of B lymphocytes into immunoglobulins-secreting plasma cells. Secreted immunoglobulins mediate the effector phase of humoral immunity, which results in the elimination of bound antigens (PubMed:20176268, PubMed:22158414). The antigen binding site is formed by the variable domain of one heavy chain, together with that of its associated light chain. Thus, each immunoglobulin has two antigen binding sites with remarkable affinity for a particular antigen. The variable domains are assembled by a process called V-(D)-J rearrangement and can then be subjected to somatic hypermutations which, after exposure to antigen and selection, allow affinity maturation for a particular antigen (PubMed:17576170, PubMed:20176268).^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

Light chain amyloidosis is a lethal disease where vital organs are damaged by the fibrillar aggregation of monoclonal light chains. lambda6a is an immunoglobulin light chain encoded by the germ line gene segment implicated in this disease. AR is a patient-derived germ line variant with a markedly low thermodynamic stability and prone to form fibrils in vitro in less than an hour. Here, we sought to stabilize this domain by mutating some residues back to the germ line sequence, and the most stabilizing mutations were the single mutant AR-F21I and the double mutant AR-F21/IV104L, both located in the hydrophobic core. While mutation Arg25Gly in 6aJL2 destabilized the domain, mutating Gly25 back to arginine in AR did not contribute to stabilization as expected. Crystallographic structures of AR and 6a-R25G were generated to explain this discrepancy. Finally, 6a-R25G crystals revealed an octameric assembly which was emulated into 6aJL2 and AR crystals by replicating their structural parameters and suggesting a common assembly pattern. This article is protected by copyright. All rights reserved.

Stabilizing an amyloidogenic lambda6 light chain variable domain.,Luna-Martinez OD, Hernandez-Santoyo A, Villalba-Velazquez MI, Sanchez-Alcala R, Fernandez-Velasco DA, Becerril B FEBS J. 2017 Sep 12. doi: 10.1111/febs.14265. PMID:28898537^[5]

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

References

↑ Teng G, Papavasiliou FN. Immunoglobulin somatic hypermutation. Annu Rev Genet. 2007;41:107-20. PMID:17576170 doi:http://dx.doi.org/10.1146/annurev.genet.41.110306.130340
↑ Schroeder HW Jr, Cavacini L. Structure and function of immunoglobulins. J Allergy Clin Immunol. 2010 Feb;125(2 Suppl 2):S41-52. doi:, 10.1016/j.jaci.2009.09.046. PMID:20176268 doi:http://dx.doi.org/10.1016/j.jaci.2009.09.046
↑ McHeyzer-Williams M, Okitsu S, Wang N, McHeyzer-Williams L. Molecular programming of B cell memory. Nat Rev Immunol. 2011 Dec 9;12(1):24-34. doi: 10.1038/nri3128. PMID:22158414 doi:http://dx.doi.org/10.1038/nri3128
↑ Lefranc MP. Immunoglobulin and T Cell Receptor Genes: IMGT((R)) and the Birth and Rise of Immunoinformatics. Front Immunol. 2014 Feb 5;5:22. doi: 10.3389/fimmu.2014.00022. eCollection 2014. PMID:24600447 doi:http://dx.doi.org/10.3389/fimmu.2014.00022
↑ Luna-Martinez OD, Hernandez-Santoyo A, Villalba-Velazquez MI, Sanchez-Alcala R, Fernandez-Velasco DA, Becerril B. Stabilizing an amyloidogenic lambda6 light chain variable domain. FEBS J. 2017 Sep 12. doi: 10.1111/febs.14265. PMID:28898537 doi:http://dx.doi.org/10.1111/febs.14265

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5ir3"

@@ Line 3: / Line 3: @@
 <StructureSection load='5ir3' size='340' side='right' caption='[[5ir3]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5ir3]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5IR3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5IR3 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5ir3]] is a 1 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=5IR3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5IR3 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3bdx|3bdx]], [[3b5g|3b5g]], [[5c9k|5c9k]], [[2w0k|2w0k]]</td></tr>
@@ Line 23: / Line 23: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Hernandez-Santoyo, A]]
 [[Category: Rodriguez-Romero, A]]

5ir3

From Proteopedia

Revision as of 10:02, 22 November 2017

Crystal structure of the recombinant highest fibrillogenic natural mutant (obtained from patient AR) derived from lambda 6 light chain variable domain

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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