Structural analysis of cross α-helical nanotubes provides insight into the designability of filamentous peptide nanomaterials
Year: 2021
Type: article
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.
Source: Nature Communications
Institutions: University of Virginia, Emory University, Dartmouth College
Language: English
Subfield: Biomaterials
Field: Materials Science
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $5,560
Funders: National Science Foundation, U.S. Department of Health and Human Services, Emory University, Dartmouth College, University of Virginia, Georgia Clinical and Translational Science Alliance, National Institutes of Health, Emory College of Arts and Sciences, Emory University, National Cancer Institute, National Institute of General Medical Sciences, Division of Materials Research, National Center for Research Resources, National Center for Advancing Translational Sciences
Awards: G1162673580, G1334251766, Computational design of novel protein binders based on structure mining and learning from data, DMREF: Collaborative Research: Helical Protein Assemblies by Design, G196810821, G2039066037, G2066468647, G2289923368, G2661436214, 300 keV Liquid Helium Robotic Microscope, G3242393064, G3460432961, G3590329166, G3714325893, Molecular Electron Microscopy Core Facility Improvements, DMREF: Collaborative Research: Helical Protein Assemblies by Design, G4440144761, G4707408251, G5369305972, II-EN: GridIron, UVA molecular electron microscopy core for the Mid-Atlantic region, G661928818, Georgia CTSA Research Supplement to Promote Diversity in Health-Related Research (Hernandez), G6743207394, G6761678178, G6767375072, G687203789, DMREF: Collaborative Research: Helical Protein Assemblies by Design, G7094225672, Understanding and using microbial conductive nanowires, G7860539593, G8243879814, G9000029981, G9000046174, G9000051629, G9000056982, MRI: Acquisition of a Circular Dichroism Spectropolarimeter
OpenAlex ID: W3123707301