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TitleHow NINJ1 mediates plasma membrane rupture and why NINJ2 cannot.
Journal, issue, pagesCell, Vol. 188, Issue 2, Page 292-302.e11, Year 2025
Publish dateJan 23, 2025
AuthorsBibekananda Sahoo / Zongjun Mou / Wei Liu / George Dubyak / Xinghong Dai /
PubMed AbstractNinjurin-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 ...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.
External linksCell / PubMed:39667936 / PubMed Central
MethodsEM (single particle)
Resolution2.75 - 3.07 Å
Structure data

40905

8sza

EMDB-40905, PDB-8sza:
Cryo-EM Structure of NINJ1 Filament at 2.75 Angstrom Resolution
Method: EM (single particle) / Resolution: 2.75 Å

40907

8szb

EMDB-40907, PDB-8szb:
Cryo-EM Structure of NINJ2 Filament at 3.07 Angstrom Resolution
Method: EM (single particle) / Resolution: 3.07 Å

Chemicals

ChemComp-CLR:
CHOLESTEROL

Source
  • homo sapiens (human)
KeywordsMEMBRANE PROTEIN / NINJ1 Filament / Plasma Membrane Rupture Protein / Cholesterol Binding Protein / Lipid Binding Protein / NINJ2 Filament / NINJ1 Paralog Protein

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