Journal article
Zinc-binding structure of a catalytic amyloid from solid-state NMR
Proceedings of the National Academy of Sciences - PNAS, v 114(24), pp 6191-6196
13 Jun 2017
PMID: 28566494
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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 self-purify and catalyze chemical reactions. They also provide attractive backbones for advanced materials. When beta-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 beta-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+.
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Details
- Title
- Zinc-binding structure of a catalytic amyloid from solid-state NMR
- Creators
- Myungwoon Lee - Massachusetts Institute of TechnologyTuo Wang - Massachusetts Institute of TechnologyOlga V. Makhlynets - Syracuse UniversityYibing Wu - University of California, San FranciscoNicholas F. Polizzi - University of California, San FranciscoHaifan Wu - University of California, San FranciscoPallavi M. Gosavi - Syracuse UniversityJan Stoehr - Univ Calif San Francisco, Inst Neurodegenerat Dis, San Francisco, CA 94158 USAIvan V. Korendovych - Syracuse UniversityWilliam F. DeGrado - University of California, San FranciscoMei Hong - Massachusetts Institute of Technology
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, v 114(24), pp 6191-6196
- Publisher
- Natl Acad Sciences
- Number of pages
- 6
- Grant note
- R01GM066976 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) GM066976; GM119634; GM54616; P01AG002132 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA 1413295 / Division Of Chemistry; National Science Foundation (NSF); NSF - Directorate for Mathematical & Physical Sciences (MPS) P01AG002132 / NATIONAL INSTITUTE ON AGING; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Chemistry
- Web of Science ID
- WOS:000403179300033
- Scopus ID
- 2-s2.0-85020818053
- Other Identifier
- 991021229894004721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology