Zinc-binding structure of a catalytic amyloid from solid-state NMR

Abstract

Significance Functional and pathological amyloid fibrils bind metal ions, but no metal-bound amyloid structures have been determined. Using solid-state NMR and structural bioinformatics, we have determined the oligomeric structure and coordination geometry of a Zn 2+ -mediated amyloid fibril that catalyzes ester hydrolysis. The peptide assembles into parallel β-sheets in which histidines bridge zinc ions to promote β-strand association in a geometry that mediates water activation for catalysis. The study demonstrates an approach for determining the structures of metalloamyloids. The resulting structure defines how metal ions can stabilize amyloids, lends support to the hypothesis that amyloids can serve as well-structured intermediates between amino acids and proteins during the evolution of life, and provides a framework for potential applications in material science.