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
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Amyloid beta-Peptides / antagonists & inhibitors*
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Amyloid beta-Peptides / metabolism
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Binding Sites
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Copper / chemistry
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Copper / pharmacology*
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Cross-Linking Reagents / chemical synthesis
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Cross-Linking Reagents / chemistry
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Cross-Linking Reagents / pharmacology*
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Disulfides / chemistry
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Disulfides / pharmacology*
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Humans
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Models, Molecular
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Molecular Chaperones / metabolism
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Polymerization
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Protein Aggregates / drug effects
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Protein Aggregation, Pathological / drug therapy*
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Protein Aggregation, Pathological / metabolism
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S100 Calcium Binding Protein beta Subunit / chemistry*
Substances
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Amyloid beta-Peptides
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Cross-Linking Reagents
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Disulfides
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Molecular Chaperones
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Protein Aggregates
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S100 Calcium Binding Protein beta Subunit
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S100B protein, human
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Copper