Structural highlights
Publication Abstract from PubMedAmyloid light-chain (AL) amyloidosis is a protein-misfolding disease characterized by accumulation of immunoglobulin light chains (LCs) into amyloid fibrils. Dimerization of a full length or variable domain (VL ) of LC serves to stabilize the native state and prevent the formation of amyloid fibrils. We here analyzed the thermodynamic properties of dimerization and unfolding reactions by nonamyloidogenic VL from REI LC or its monomeric Y96K mutant using sedimentation velocity and circular dichroism. The data indicate that the equilibrium shifts to native dimerization for wild-type REI VL by elevating temperature due to the negative enthalpy change for dimer dissociation (-81.2 kJ.mol-1 ). The Y96K mutation did not affect the stability of the monomeric native state but increased amyloidogenicity. These results suggest that the heat-induced native homodimerization is the major factor preventing amyloid formation by wild-type REI VL . Heat-induced native oligomerization may be an efficient strategy to avoid the formation of misfolded aggregates particularly for thermostable proteins that are used at elevated temperatures under conditions where other proteins tend to misfold. DATABASE: Structural data are available in the Protein Data Bank under the accession numbers 5XP1 and 5XQY. Heat-induced native dimerization prevents amyloid formation by variable domain from immunoglobulin light-chain REI.,Nawata M, Tsutsumi H, Kobayashi Y, Unzai S, Mine S, Nakamura T, Uegaki K, Kamikubo H, Kataoka M, Hamada D FEBS J. 2017 Sep;284(18):3114-3127. doi: 10.1111/febs.14181. Epub 2017 Aug 13. PMID:28736891[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||
This page was last modified 08:10, 22 November 2023.