5UGK

Zinc-Binding Structure of a Catalytic Amyloid from Solid-State NMR Spectroscopy

Summary for 5UGK

• Entry DOI: 10.2210/pdb5ugk/pdb
• NMR Information: BMRB: 30227
• Descriptor: ILE-HIS-VAL-HIS-LEU-GLN-ILE, ZINC ION (2 entities in total)
• Functional Keywords: amyloid, metal binding protein
• Biological source: synthetic construct
• Total number of polymer chains: 12
• Total formula weight: 11117.41

Authors

Lee, M.,Wang, T.,Makhlynets, O.V.,Wu, Y.,Polizzi, N.,Wu, H.,Gosavi, P.M.,Korendovych, I.V.,DeGrado, W.F.,Hong, M. (deposition date: 2017-01-09, release date: 2017-05-31, Last modification date: 2024-05-15)

Primary citation

Lee, M.,Wang, T.,Makhlynets, O.V.,Wu, Y.,Polizzi, N.F.,Wu, H.,Gosavi, P.M.,Stohr, J.,Korendovych, I.V.,DeGrado, W.F.,Hong, M.
Zinc-binding structure of a catalytic amyloid from solid-state NMR.
Proc. Natl. Acad. Sci. U.S.A., 114:6191-6196, 2017

PubMed 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 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 Zn-binding histidines with binding geometries unusual in proteins. Each Zn 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 Zn 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 Zn.

PubMed: 28566494
DOI: 10.1073/pnas.1706179114

Experimental method

SOLID-STATE NMR