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Author Notes:

Edward H. Egelman, Email: egelman@virginia.edu

Vincent P. Conticello, vcontic@emory.edu

Conceptualization, F.W., O.G., E.H.E., and V.P.C.; methodology, F.W., E.H.E., and V.P.C.; investigation, F.W., O.G., S.W., T.O., and X.Z.; supervision, E.H.E. and V.P.C.; validation, F.W. and E.H.E.; visualization, F.W., E.H.E., and V.P.C.; writing – original draft, F.W., E.H.E., and V.P.C.; writing – review and editing, F.W., E.H.E., and V.P.C.; funding acquisition, F.W., E.H.E., and V.P.C.

Cryo-EM imaging was conducted at the Molecular Electron Microscopy Core facility at the University of Virginia, which is supported by the School of Medicine and built with National Institutes of Health (NIH) grant G20-RR31199. In addition, the Titan Krios (SIG S10-RR025067) and K3/GIF (U24-GM116790) were purchased, in part or in full, with the designated NIH grants. This study was supported by the Robert P. Apkarian Integrated Electron Microscopy Core (IEMC) at Emory University, which is subsidized by the School of Medicine and Emory College of Arts and Sciences. Negative stain TEM images were acquired on a Hitachi HT7700 120kV TEM at Emory University, which was supported by the Georgia Clinical and Translational Science Alliance under award number UL1TR002378. The content is solely the responsibility of the authors and does not necessarily reflect the official views of the NIH. This research was supported by grants from the National Science Foundation (NSF) (DMR-1534317) to V.P.C., the NIH (GM138756) to F.W., and the NIH (GM122510) to E.H.E. The circular dichroism spectropolarimeter was acquired through funding from an NSF grant (DBI-1726544). This research used resources of the Advanced Photon Source, a US Department of Energy (DOE) Office of Science User Facility, operated for the DOE Office of Science by Argonne National Laboratory under contract no. DE-AC02-06CH11357. The authors thank Dr. Gevorg Grigoryan for useful discussions

The authors declare no competing interests.

Subject:

Deterministic chaos in the self-assembly of β sheet nanotubes from an amphipathic oligopeptide

Tools:

Journal Title:

Matter

Volume:

Volume 4, Number 10

Publisher:

, Pages 3217-3231

Type of Work:

Article | Post-print: After Peer Review

Abstract:

The self-assembly of designed peptides into filaments and other higher-order structures has been the focus of intense interest because of the potential for creating new biomaterials and biomedical devices. These peptide assemblies have also been used as models for understanding biological processes, such as the pathological formation of amyloid. We investigate the assembly of an octapeptide sequence, Ac-FKFEFKFE-NH2, motivated by prior studies that demonstrated that this amphipathic β strand peptide self-assembled into fibrils and biocompatible hydrogels. Using high-resolution cryoelectron microscopy (cryo-EM), we are able to determine the atomic structure for two different coexisting forms of the fibrils, containing four and five β sandwich protofilaments, respectively. Surprisingly, the inner walls in both forms are parallel β sheets, while the outer walls are antiparallel β sheets. Our results demonstrate the chaotic nature of peptide self-assembly and illustrate the importance of cryo-EM structural analysis to understand the complex phase behavior of these materials at near-atomic resolution.

Copyright information:

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/).
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