8Q4L
GBP1 bound by 14-3-3sigma
Summary for 8Q4L
| Entry DOI | 10.2210/pdb8q4l/pdb |
| EMDB information | 18149 |
| Descriptor | Guanylate-binding protein 1, 14-3-3 protein sigma (2 entities in total) |
| Functional Keywords | protein complex, phosphorylation, immune system |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 3 |
| Total formula weight | 118554.46 |
| Authors | Pfleiderer, M.M.,Liu, X.,Fisch, D.,Anastasakou, E.,Frickel, E.M.,Galej, W.P. (deposition date: 2023-08-07, release date: 2023-10-11, Last modification date: 2023-10-18) |
| Primary citation | 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 Cited by 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: 37797010DOI: 10.1126/science.adg2253 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (5.12 Å) |
Structure validation
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