View source for 4unu


==MCG - a dimer of lambda variable domains==
<StructureSection load='4unu' size='340' side='right'caption='[[4unu]], [[Resolution|resolution]] 0.95&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4unu]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4UNU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4UNU FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 0.95&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=15P:POLYETHYLENE+GLYCOL+(N=34)'>15P</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4unu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4unu OCA], [https://pdbe.org/4unu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4unu RCSB], [https://www.ebi.ac.uk/pdbsum/4unu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4unu ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/LV208_HUMAN LV208_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).<ref>PMID:17576170</ref> <ref>PMID:20176268</ref> <ref>PMID:22158414</ref> <ref>PMID:24600447</ref> 
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== Publication Abstract from PubMed ==
Systemic light-chain amyloidosis is a lethal disease characterized by excess immunoglobulin light-chains and light-chain fragments composed of variable domains, which aggregate into amyloid fibers. These fibers accumulate and damage organs. Some light-chains induce formation of amyloid fibers while others do not, making it unclear what distinguishes amyloid formers from non-formers. One mechanism by which sequence variation may reduce propensity to form amyloid fibers is by shifting the equilibrium toward an amyloid-resistant quaternary structure. Here we identify the monomeric form of the Mcg immunoglobulin light-chain variable domain as the quaternary unit required for amyloid fiber assembly. Dimers of Mcg variable domains remain stable and soluble, yet become prone to assemble into amyloid fibers upon disassociation into monomers.

Formation of Amyloid Fibers by Monomeric Light-chain Variable Domains.,Brumshtein B, Esswein SR, Landau M, Ryan CM, Whitelegge JP, Phillips ML, Cascio D, Sawaya MR, Eisenberg DS J Biol Chem. 2014 Aug 19. pii: jbc.M114.585638. PMID:25138218<ref>PMID:25138218</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4unu" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Brumshtein B]]
[[Category: Casio D]]
[[Category: Eisenberg DS]]
[[Category: Esswein SR]]
[[Category: Landau M]]
[[Category: Ryan C]]
[[Category: Sawaya MR]]
[[Category: Whitelegge J]]