How guanylate-binding proteins achieve assembly-stimulated processive cleavage of GTP to GMP
- 1 March 2006
- journal article
- Published by Springer Science and Business Media LLC in Nature
- Vol. 440 (7080), 101-104
- https://doi.org/10.1038/nature04510
Abstract
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.This publication has 30 references indexed in Scilit:
- The dynamin superfamily: universal membrane tubulation and fission molecules?Nature Reviews Molecular Cell Biology, 2004
- The guanylate binding protein-1 GTPase controls the invasive and angiogenic capability of endothelial cells through inhibition of MMP-1 expressionThe EMBO Journal, 2003
- The helical domain of GBP-1 mediates the inhibition of endothelial cell proliferation by inflammatory cytokinesThe EMBO Journal, 2001
- Triphosphate structure of guanylate-binding protein 1 and implications for nucleotide binding and GTPase mechanismThe EMBO Journal, 2000
- Structure of human guanylate-binding protein 1 representing a unique class of GTP-binding proteinsNature, 2000
- Nucleotide-binding characteristics of human guanylate-binding protein 1 (hGBP1) and identification of the third GTP-binding motifJournal of Molecular Biology, 1999
- Interferon-Induced Guanylate Binding Protein-1 (GBP-1) Mediates an Antiviral Effect against Vesicular Stomatitis Virus and Encephalomyocarditis VirusVirology, 1999
- HOW CELLS RESPOND TO INTERFERONSAnnual Review of Biochemistry, 1998
- GTPase properties of the interferon‐induced human guanylate‐binding protein 2FEBS Letters, 1996
- Interferon-induced guanylate-binding proteins lack an N(T)KXD consensus motif and bind GMP in addition to GDP and GTP.Molecular and Cellular Biology, 1991