9MFU

Cryo-EM of helical fibers formed by (NAP)FFGPQYQP

Summary for 9MFU

• Entry DOI: 10.2210/pdb9mfu/pdb
• EMDB information: 48237
• Descriptor: (I7L)FFGPQYQP (1 entity in total)
• Functional Keywords: peptide fiber, helical polymer, protein fibril
• Biological source: synthetic construct
• Total number of polymer chains: 7
• Total formula weight: 8058.87

Authors

Zia, A.,Qiao, Y.,Xu, B.,Wang, F. (deposition date: 2024-12-10, release date: 2025-05-07, Last modification date: 2025-05-14)

Primary citation

Qiao, Y.,Zia, A.,Shy, A.,Wu, G.,Chu, M.,Liu, Z.,Wang, F.,Xu, B.
Intrinsically Disordered Peptide Nanofibers from A Structured Motif within Proteins.
Angew.Chem.Int.Ed.Engl., :e202425456-e202425456, 2025

PubMed Abstract: Intrinsically disordered regions (IDRs) are ubiquitous in proteins, orchestrating complex cellular signaling through higher-order protein assemblies. However, the properties and functions of intrinsically disordered peptide (IDP) assemblies are largely underexplored. This work unveiled a facile strategy for engineering IDP assemblies. We demonstrate that conjugating a structured motif derived from a protein's phosphorylation site to a self-assembling tripeptide unexpectedly yields self-assembled nanofibers with intrinsic disorder. Specifically, by using a glycine linker to attach a pentapeptide derived from a phosphorylation site within a random coil region of SRC kinase to the C-terminus of a widely used self-assembling enabler, we generated a phosphorylated octapeptide. The octapeptide exhibits cell compatibility and forms a hydrogel upon dephosphorylation of the phosphooctapeptide. Cryo-electron microscopy (cryo-EM) structural analysis of the nanofibers reveals that the peptides adopt two types of helical arrangements but exhibit intrinsic disorder at the periphery of the nanofibers. The hydrogels exhibit decreased protein adsorption with increasing peptide concentration. This study represents the first instance of a structured random coil within a protein transitioning into an intrinsically disordered state within self-assembled peptide nanofibers, expanding the pool of peptide sequences for IDPs and providing valuable insights for the engineering of peptide nanofibers with intrinsic disorder for the development of cell-compatible biomaterials.

PubMed: 40294067
DOI: 10.1002/anie.202425456

Experimental method

ELECTRON MICROSCOPY (2.87 Å)