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Formation of amyloid fibers by monomeric light chain variable domains.
J Biol Chem. 2014 Oct 3;289(40):27513-25. doi: 10.1074/jbc.M114.585638
Brumshtein B, Esswein SR, Landau M, Ryan CM, Whitelegge JP, Phillips ML, Cascio D, Sawaya MR, Eisenberg DS
Abstract:
.....Some light chains induce formation of amyloid fibers, whereas 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.
PMID: 25138218
Tags: AL amyloidosis