Hierarchical Assembly of Intrinsically Disordered Short Peptides

Jiaqi Guo, Shane T. Rich-New, Yimeng Huang, Weiyi Tan, Hongjian He, Meihui Yi, Xixiang Zhang, Edward H. Egelman, Fengbin Wang, Bing Xu

Research output: Contribution to journalArticlepeer-review


The understanding on how short peptide assemblies transit from disorder to order remains limited due to the lack of atomistic structures. Here we report cryo-EM structure of the nanofibers short intrinsically disordered peptides (IDPs). Upon lowering pH or adding calcium ions, the IDP transitions from individual nanoparticles to nanofibers containing an aromatic core and a disordered periphery comprised of 2 to 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.
Original languageEnglish (US)
JournalAccepted by Chem
StatePublished - Apr 28 2023

Bibliographical note

KAUST Repository Item: Exported on 2023-05-01
Acknowledgements: 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.


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