2d4h
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Crystal-structure of the N-terminal large GTPase Domain of human Guanylate Binding protein 1 (hGBP1) in complex with GMP
OverviewOverview
Interferons are immunomodulatory cytokines that mediate anti-pathogenic, and anti-proliferative effects in cells. Interferon-gamma-inducible human, guanylate binding protein 1 (hGBP1) belongs to the family of, dynamin-related large GTP-binding proteins, which share biochemical, properties not found in other families of GTP-binding proteins such as, nucleotide-dependent oligomerization and fast cooperative GTPase activity., hGBP1 has an additional property by which it hydrolyses GTP to GMP in two, consecutive cleavage reactions. Here we show that the isolated, amino-terminal G domain of hGBP1 retains the main enzymatic properties of, the full-length protein and can cleave GDP directly. Crystal structures of, the N-terminal G domain trapped at successive steps along the reaction, pathway and biochemical data reveal the molecular basis for, nucleotide-dependent homodimerization and cleavage of GTP. Similar to, effector binding in other GTP-binding proteins, homodimerization is, regulated by structural changes in the switch regions. Homodimerization, generates a conformation in which an arginine finger and a serine are, oriented for efficient catalysis. Positioning of the substrate for the, second hydrolysis step is achieved by a change in nucleotide conformation, at the ribose that keeps the guanine base interactions intact and, positions the beta-phosphates in the gamma-phosphate-binding site.
About this StructureAbout this Structure
2D4H is a Single protein structure of sequence from Homo sapiens with 5GP as ligand. Full crystallographic information is available from OCA.
ReferenceReference
How guanylate-binding proteins achieve assembly-stimulated processive cleavage of GTP to GMP., Ghosh A, Praefcke GJ, Renault L, Wittinghofer A, Herrmann C, Nature. 2006 Mar 2;440(7080):101-4. PMID:16511497
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