Zinc-binding structure of a catalytic amyloid from solid-state NMR
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1.9 MB
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Checksum (MD5)
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Author(s)
Lee, Myungwoon
Wang, Tuo
Makhlynets, Olga V.
Wu, Yibing
Polizzi, Nicholas F.
Wu, Haifan
Gosavi, Pallavi M.
Stöhr, Jan
Korendovych, Ivan V.
DeGrado, William F.
Date Issued
June 2017
Journal
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences (U.S.)
Citation
Lee, Myungwoon et al. “Zinc-Binding Structure of a Catalytic Amyloid from Solid-State NMR.” Proceedings of the National Academy of Sciences 114, 24 (May 2017): 6191–6196 © 2017 National Academy of Sciences
Version
Final published version
Abstract
Throughout biology, amyloids are key structures in both functional proteins and the end product of pathologic protein misfolding. Amyloids might also represent an early precursor in the evolution of life because of their small molecular size and their ability to selfpurify and catalyze chemical reactions. They also provide attractive backbones for advanced materials. When β-strands of an amyloid are arranged parallel and in register, side chains from the same position of each chain align, facilitating metal chelation when the residues are good ligands such as histidine. High-resolution structures of metalloamyloids are needed to understand the molecular bases of metal-amyloid interactions. Here we combine solid-state NMR and structural bioinformatics to determine the structure of a zinc-bound metalloamyloid that catalyzes ester hydrolysis. The peptide forms amphiphilic parallel β-sheets that assemble into stacked bilayers with alternating hydrophobic and polar interfaces. The hydrophobic interface is stabilized by apolar side chains from adjacent sheets, whereas the hydrated polar interface houses the Zn²⁺-binding histidines with binding geometries unusual in proteins. Each Zn²⁺ has two bis-coordinated histidine ligands, which bridge adjacent strands to form an infinite metal-ligand chain along the fibril axis. A third histidine completes the protein ligand environment, leaving a free site on the Zn²⁺ for water activation. This structure defines a class of materials, which we call metal-peptide frameworks. The structure reveals a delicate interplay through which metal ions stabilize the amyloid structure, which in turn shapes the ligand geometry and catalytic reactivity of Zn²⁺. Keywords: magic angle spinning; metalloprotein; histidine; metal-peptide framework
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
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DOI of Published Version
https://doi.org/10.1073/PNAS.1706179114
