439 research outputs found
Hierarchical assembly of intrinsically disordered short peptides
The understanding of how short peptide assemblies transit from disorder to order remains limited due to the lack of atomistic structures. Here, we report the cryo-EM structure of the nanofibers short intrinsically disordered peptides (IDPs). On lowering pH or adding calcium ions, the IDP transitions from individual nanoparticles to nanofibers containing an aromatic core and a disordered periphery were composed of 2–5 amino acids. Protonating the phosphate or adding more metal ions further assembles the nanofibers into filament bundles. The assemblies of the IDP analogs with controlled chemistry, such as phosphorylation site, hydrophobic interactions, and sequences, indicate that metal ions interact with the flexible periphery of the nanoparticles of the IDPs to form fibrils and enhance the interfibrillar interactions to form filament bundles. Illustrating that an IDP self-assembles from disorder to order, this work offers atomistic molecular insights to understand assemblies of short peptides driven by noncovalent interactions.This work is partially supported by NIH CA142746 (B.X.), GM122510 (E.H.E.), GM138756 (F.W.), and NSF DMR-2011846 (B.X.). This research was, in part, supported by the National Cancer Institute's National Cryo-EM Facility at the Frederick National Laboratory for Cancer Research under contract 75N91019D00024. The cryo-EM imaging was, in part, done at the Molecular Electron Microscopy Core Facility at the University of Virginia. The cryo-EM screening process was, in part, supported by the O'Neal Comprehensive Cancer Center at the University of Alabama Birmingham. B.X. and J.G. conceived the study. J.G. under the supervision of B.X. designed and performed chemical synthesis, generated images of characterization, and analyzed the results. C.L. under the supervision of X.Z. performed STEM. Y.H. and M.Y. assisted in chemical synthesis. H.H. and W.T. performed LC-MS analysis. S.T.R.-N. and F.W. performed cryo-EM reconstructions and model building. J.G. S.T.R. E.H.E. F.W. and B.X. wrote the manuscript with input from all authors. The authors declare no competing interests
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