8SZA

Cryo-EM Structure of NINJ1 Filament at 2.75 Angstrom Resolution

Summary for 8SZA

• Entry DOI: 10.2210/pdb8sza/pdb
• EMDB information: 40905
• Descriptor: Ninjurin-1, CHOLESTEROL (2 entities in total)
• Functional Keywords: ninj1 filament, plasma membrane rupture protein, cholesterol binding protein, lipid binding protein, membrane protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 6
• Total formula weight: 117981.30

Authors

Sahoo, B.,Dai, X. (deposition date: 2023-05-29, release date: 2023-06-14, Last modification date: 2025-02-05)

Primary citation

Sahoo, B.,Mou, Z.,Liu, W.,Dubyak, G.,Dai, X.
How NINJ1 mediates plasma membrane rupture and why NINJ2 cannot.
Cell, 188:292-302.e11, 2025

PubMed Abstract: Ninjurin-1 (NINJ1) is an active executioner of plasma membrane rupture (PMR), a process previously thought to be a passive osmotic lysis event in lytic cell death. Ninjurin-2 (NINJ2) is a close paralog of NINJ1 but cannot mediate PMR. Using cryogenic electron microscopy (cryo-EM), we show that NINJ1 and NINJ2 both assemble into linear filaments that are hydrophobic on one side but hydrophilic on the other. This structural feature and other evidence point to a PMR mechanism by which NINJ1 filaments wrap around and solubilize membrane fragments and, less frequently, form pores in the plasma membrane. In contrast to the straight NINJ1 filament, the NINJ2 filament is curved toward the intracellular space, preventing its circularization or even assembly on a relatively flat membrane to mediate PMR. Mutagenesis studies further demonstrate that the NINJ2 filament curvature is induced by strong association with lipids, particularly a cholesterol molecule, at the cytoplasmic leaflet of the lipid bilayer.

PubMed: 39667936
DOI: 10.1016/j.cell.2024.11.021

Experimental method

ELECTRON MICROSCOPY (2.75 Å)