9NWR

Cryo-EM of Class-2 of YM1P nanotube

This is a non-PDB format compatible entry.

Summary for 9NWR

• Entry DOI: 10.2210/pdb9nwr/pdb
• EMDB information: 49891
• Descriptor: YM1P (1 entity in total)
• Functional Keywords: d-peptide, peptide-fiber, helical, protein fibril
• Biological source: synthetic construct
• Total number of polymer chains: 2
• Total formula weight: 1491.42

Authors

Yi, M.,Zia, A.,Egelman, E.H.,Xu, B.,Wang, F. (deposition date: 2025-03-24, release date: 2026-04-15)

Primary citation

Yi, M.,Guo, J.,Zia, A.,Guo, W.,Tachiyama, S.,Ashton-Rickardt, G.,Tan, W.,Qiao, Y.,Gong, Y.,Egelman, E.H.,Liu, J.,Wang, F.,Xu, B.
Cryo-Structural Insights into Enzymatic Peptide Self-Assembly Driving Extrinsic Lytic Cell Death.
J.Am.Chem.Soc., 2026

PubMed Abstract: Programmed lytic cell death, including pyroptosis and necroptosis, involves intracellular enzymes that form membrane-rupturing pores. Tumor-associated ectoenzymes such as alkaline phosphatase (ALP), however, offer the potential to initiate lytic death extrinsically. Here, we design a phospho-biphenyl-capped peptide precursor that is selectively dephosphorylated by ALP on cancer cell surfaces, triggering enzyme-instructed peptide self-assembly (EISA) into in situ peptide filaments. These supramolecular filaments physically breach the plasma membrane, overwhelm ESCRT-dependent membrane repair, and induce catastrophic calcium influx, cytoskeletal collapse, and organelle dysfunction. While cryo-EM uncovers 2.5-2.9 Å resolution details of ordered dimeric packing that underlies their mechanical rigidity and membrane-rupturing capability, cryo-electron tomography (cryo-ET) reveals the filament penetration of the plasma membrane in live cells. By reprogramming ALP from an immune checkpoint ectoenzyme into a pro-death catalyst, this work establishes a molecular mechanism linking enzymatic catalysis to supramolecular order and membrane failure. More broadly, it outlines a supramolecular chemical-biology framework in which enzyme-triggered assemblies function as programmable executors of cell death.

PubMed: 41875418
DOI: 10.1021/jacs.5c23283

Experimental method

ELECTRON MICROSCOPY (2.8 Å)