8SZB

Cryo-EM Structure of NINJ2 Filament at 3.07 Angstrom Resolution

8SZB の概要

• エントリーDOI: 10.2210/pdb8szb/pdb
• EMDBエントリー: 40907
• 分子名称: Ninjurin-2, CHOLESTEROL (2 entities in total)
• 機能のキーワード: ninj2 filament, ninj1 paralog protein, cholesterol binding protein, lipid binding protein, membrane protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 114010.61

構造登録者

Sahoo, B.,Dai, X. (登録日: 2023-05-29, 公開日: 2023-06-14, 最終更新日: 2025-02-05)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (3.07 Å)