GBP1

Guanylate-binding protein 1

Action

Hydrolyzes GTP to GMP in 2 consecutive cleavage reactions:
GTP + H2O = GDP + phosphate

Exhibits antiviral activity against influenza virus.

Promote oxidative killing and deliver antimicrobial peptides to autophagolysosomes, providing broad host protection against different pathogen classes.

GBP-1 is both necessary and sufficient for the inhibitory effects of IFN-γ on cell proliferation, migration, and invasion, as shown in endothelial cells and epithelial tumor cells (17, 19, 34,–37 in [1]).

Purified GBP-1 and actin bound to each other, and this interaction was sufficient to impair the formation of actin filaments in vitro [1].

Cosedimentation and band shift analyses demonstrated that GBP-1 binds robustly to globular actin and slightly to filamentous actin. This indicated that GBP-1 may induce actin remodeling via globular actin sequestering and/or filament capping.[1]..

GBP-1 colocalized with actin at the subcellular level and was both necessary and sufficient for the extensive remodeling of the fibrous actin structure observed in IFN-γ-exposed cells. These effects were dependent on the oligomerization and the GTPase activity of GBP-1[1].

An artificial backwards-moving myosin from three pre-existing molecular building blocks:
- a forward-moving class I myosin motor domain,
- a directional inverter formed by a four-helix bundle segment of human guanylate-binding protein-1
- an artificial lever arm formed by two alpha-actinin repeats.
Reverse-direction movement of myosins can be achieved simply by rotating the direction of the lever arm 180 degrees [2].

Pathways

GBP-1 is a major IFN-γ-induced protein in eukaryotic cells (22, 66 in [1]).

Diseases

Chronic Active Epstein-Barr Virus Infection and Aneurysmal Bone Cysts.

References

1. Ostler N, Britzen-Laurent N, Liebl A, Naschberger E, Lochnit G, Ostler M, Forster F, Kunzelmann P, Ince S, Supper V, Praefcke GJ, Schubert DW, Stockinger H, Herrmann C, and Stürzl M. Gamma interferon-induced guanylate binding protein 1 is a novel actin cytoskeleton remodeling factor. Mol Cell Biol. 2014 Jan;34(2):196-209. DOI:10.1128/MCB.00664-13 |
2. Tsiavaliaris G, Fujita-Becker S, and Manstein DJ. Molecular engineering of a backwards-moving myosin motor. Nature. 2004 Feb 5;427(6974):558-61. DOI:10.1038/nature02303 |

Expression

Upregulated - after 1 hour after exercises and after training.