8Q4L

GBP1 bound by 14-3-3sigma

8Q4L の概要

• エントリーDOI: 10.2210/pdb8q4l/pdb
• EMDBエントリー: 18149
• 分子名称: Guanylate-binding protein 1, 14-3-3 protein sigma (2 entities in total)
• 機能のキーワード: protein complex, phosphorylation, immune system
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 118554.46

構造登録者

Pfleiderer, M.M.,Liu, X.,Fisch, D.,Anastasakou, E.,Frickel, E.M.,Galej, W.P. (登録日: 2023-08-07, 公開日: 2023-10-11, 最終更新日: 2023-10-18)

主引用文献

Fisch, D.,Pfleiderer, M.M.,Anastasakou, E.,Mackie, G.M.,Wendt, F.,Liu, X.,Clough, B.,Lara-Reyna, S.,Encheva, V.,Snijders, A.P.,Bando, H.,Yamamoto, M.,Beggs, A.D.,Mercer, J.,Shenoy, A.R.,Wollscheid, B.,Maslowski, K.M.,Galej, W.P.,Frickel, E.M.
PIM1 controls GBP1 activity to limit self-damage and to guard against pathogen infection.
Science, 382:eadg2253-eadg2253, 2023

PubMed Abstract: Disruption of cellular activities by pathogen virulence factors can trigger innate immune responses. Interferon-γ (IFN-γ)-inducible antimicrobial factors, such as the guanylate binding proteins (GBPs), promote cell-intrinsic defense by attacking intracellular pathogens and by inducing programmed cell death. Working in human macrophages, we discovered that GBP1 expression in the absence of IFN-γ killed the cells and induced Golgi fragmentation. IFN-γ exposure improved macrophage survival through the activity of the kinase PIM1. PIM1 phosphorylated GBP1, leading to its sequestration by 14-3-3σ, which thereby prevented GBP1 membrane association. During infection, the virulence protein TgIST interfered with IFN-γ signaling and depleted PIM1, thereby increasing GBP1 activity. Although infected cells can restrain pathogens in a GBP1-dependent manner, this mechanism can protect uninfected bystander cells. Thus, PIM1 can provide a bait for pathogen virulence factors, guarding the integrity of IFN-γ signaling.

PubMed: 37797010
DOI: 10.1126/science.adg2253

実験手法

ELECTRON MICROSCOPY (5.12 Å)