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Epigallocatechin-3-gallate Inhibits Cu(II)-Induced β-2-Microglobulin Amyloid Formation by Binding to the Edge of Its β-Sheets.

Abstract：

:Epigallocatechin-3-gallate (EGCG) is a catechin found in green tea that can inhibit the amyloid formation of a wide variety of proteins. EGCG's ability to prevent or redirect the amyloid formation of so many proteins may reflect a common mechanism of action, and thus, greater molecular-level insight into how it exerts its effect could have broad implications. Here, we investigate the molecular details of EGCG's inhibition of the protein β-2-microglobulin (β2m), which forms amyloids in patients undergoing long-term dialysis treatment. Using size-exclusion chromatography and a collection of mass spectrometry-based techniques, we find that EGCG prevents Cu(II)-induced β2m amyloid formation by diverting the normal progression of preamyloid oligomers toward the formation of spherical, redissolvable aggregates. EGCG exerts its effect by binding with a micromolar affinity (Kd ≈ 5 μM) to the β2m monomer on the edge of two β-sheets near the N-terminus. This interaction destabilizes the preamyloid dimer and prevents the formation of a tetramer species previously shown to be essential for Cu(II)-induced β2m amyloid formation. EGCG's binding at the edge of the β-sheets in β2m is consistent with a previous hypothesis that EGCG generally prevents amyloid formation by binding cross-β-sheet aggregation intermediates.

journal_name

Biochemistry

journal_title

Biochemistry

authors

Marcinko TM,Drews T,Liu T,Vachet RW

doi

10.1021/acs.biochem.0c00043

subject

Has Abstract

pub_date

2020-03-17 00:00:00

pages

1093-1103

issue

10

eissn

0006-2960

issn

1520-4995

journal_volume

59

pub_type

杂志文章

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