Cu2+-binding to S100B triggers polymerization of disulfide cross-linked tetramers with enhanced chaperone activity against amyloid-β aggregation

Chem Commun (Camb). 2021 Jan 14;57(3):379-382. doi: 10.1039/d0cc06842j.

Abstract

S100B is an extracellular protein implicated in Alzheimer's Disease and a suppressor of amyloid-β 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.

MeSH terms

  • Amyloid beta-Peptides / antagonists & inhibitors*
  • Amyloid beta-Peptides / metabolism
  • Binding Sites
  • Copper / chemistry
  • Copper / pharmacology*
  • Cross-Linking Reagents / chemical synthesis
  • Cross-Linking Reagents / chemistry
  • Cross-Linking Reagents / pharmacology*
  • Disulfides / chemistry
  • Disulfides / pharmacology*
  • Humans
  • Models, Molecular
  • Molecular Chaperones / metabolism
  • Polymerization
  • Protein Aggregates / drug effects
  • Protein Aggregation, Pathological / drug therapy*
  • Protein Aggregation, Pathological / metabolism
  • S100 Calcium Binding Protein beta Subunit / chemistry*

Substances

  • Amyloid beta-Peptides
  • Cross-Linking Reagents
  • Disulfides
  • Molecular Chaperones
  • Protein Aggregates
  • S100 Calcium Binding Protein beta Subunit
  • S100B protein, human
  • Copper