6U2K

EM structure of MPEG-1 (L425K, alpha conformation) soluble pre-pore complex

6U2K の概要

• エントリーDOI: 10.2210/pdb6u2k/pdb
• EMDBエントリー: 20616 20617 20619 20620 20621 20622 20623
• 分子名称: Macrophage-expressed gene 1 protein, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose (2 entities in total)
• 機能のキーワード: mpeg-1/perforin-2, macpf, macrophage, pore forming proteins, immunity, immune system
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 71974.95

構造登録者

Pang, S.S.,Bayly-Jones, C. (登録日: 2019-08-20, 公開日: 2019-09-25, 最終更新日: 2024-10-23)

主引用文献

Pang, S.S.,Bayly-Jones, C.,Radjainia, M.,Spicer, B.A.,Law, R.H.P.,Hodel, A.W.,Parsons, E.S.,Ekkel, S.M.,Conroy, P.J.,Ramm, G.,Venugopal, H.,Bird, P.I.,Hoogenboom, B.W.,Voskoboinik, I.,Gambin, Y.,Sierecki, E.,Dunstone, M.A.,Whisstock, J.C.
The cryo-EM structure of the acid activatable pore-forming immune effector Macrophage-expressed gene 1.
Nat Commun, 10:4288-4288, 2019

PubMed Abstract: Macrophage-expressed gene 1 (MPEG1/Perforin-2) is a perforin-like protein that functions within the phagolysosome to damage engulfed microbes. MPEG1 is thought to form pores in target membranes, however, its mode of action remains unknown. We use cryo-Electron Microscopy (cryo-EM) to determine the 2.4 Å structure of a hexadecameric assembly of MPEG1 that displays the expected features of a soluble prepore complex. We further discover that MPEG1 prepore-like assemblies can be induced to perforate membranes through acidification, such as would occur within maturing phagolysosomes. We next solve the 3.6 Å cryo-EM structure of MPEG1 in complex with liposomes. These data reveal that a multi-vesicular body of 12 kDa (MVB12)-associated β-prism (MABP) domain binds membranes such that the pore-forming machinery of MPEG1 is oriented away from the bound membrane. This unexpected mechanism of membrane interaction suggests that MPEG1 remains bound to the phagolysosome membrane while simultaneously forming pores in engulfed bacterial targets.

PubMed: 31537793
DOI: 10.1038/s41467-019-12279-2

実験手法

ELECTRON MICROSCOPY (2.93 Å)