Structural analysis of cross α-helical nanotubes provides insight into the designability of filamentous peptide nanomaterials

• Type of Material: Article
• Authors: Fengbin Wang, University of Virginia; Ordy Gnewou, Emory University; Charles Modlin, Emory University; Leticia C Beltran, University of Virginia; Chunfu Xu, Emory University; Zhangli Su, University of Virginia; Puneet Juneja, Emory University; Gevorg Grigoryan, Dartmouth College; Edward H Egelman, University of Virginia; Vincent Conticello, Emory University
• Language: English
• Date: 2021-12-01
• Publisher: Springer Nature
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2021
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41467-020-20689-w
• Title of Journal or Parent Work: Nature Communications
• Volume: 12
• Issue: 1
• Start Page: 407
• End Page: 407
• Grant/Funding Information: This research was supported by grants from the NSF (DMR-1534317 (V.P.C.), DMR-1533958 (E.H.E.) and DMR-1534246 (G.G.)) and NIH (GM132117 (G.G.)). The circular dichroism spectropolarimeter was acquired through funding from an NSF grant (DBI-1726544). Dartmouth cluster computer infrastructure was supported by NSF grant CNS-1205521.
• Keywords: Arginine; Nanotubes, Peptide; Cryoelectron Microscopy; Protein Conformation, alpha-Helical; Structure-Activity Relationship; Models, Molecular
• Research Categories: Chemistry, Physical; Biology, Molecular; Chemistry, Biochemistry; Chemistry, General; Computer Science

Abstract

The exquisite structure-function correlations observed in filamentous protein assemblies provide a paradigm for the design of synthetic peptide-based nanomaterials. However, the plasticity of quaternary structure in sequence-space and the lability of helical symmetry present significant challenges to the de novo design and structural analysis of such filaments. Here, we describe a rational approach to design self-assembling peptide nanotubes based on controlling lateral interactions between protofilaments having an unusual cross-α supramolecular architecture. Near-atomic resolution cryo-EM structural analysis of seven designed nanotubes provides insight into the designability of interfaces within these synthetic peptide assemblies and identifies a non-native structural interaction based on a pair of arginine residues. This arginine clasp motif can robustly mediate cohesive interactions between protofilaments within the cross-α nanotubes. The structure of the resultant assemblies can be controlled through the sequence and length of the peptide subunits, which generates synthetic peptide filaments of similar dimensions to flagella and pili.