Cu2+-Binding To S100b Triggers Polymerization Of Disulfide Cross-Linked Tetramers With Enhanced Chaperone Activity Against Amyloid-Beta Aggregation

S100B is an extracellular protein implicated in Alzheimer's Disease and a suppressor of amyloid-beta aggregation. Herein we report a mechanism tying Cu2+ binding to a change in assembly state yielding disulfide cross-linked oligomers with higher anti-aggregation activity. This chemical control of chaperone function illustrates a regulatory process relevant under metal and proteostasis dysfunction as in neurodegeneration.