title: Structure of human guanylate-binding protein 1 representing a unique class of GTP-binding proteins.
abstract: Interferon-gamma is an immunomodulatory substance that induces the expression of many genes to orchestrate a cellular response and establish the antiviral state of the cell. Among the most abundant antiviral proteins induced by interferon-gamma are guanylate-binding proteins such as GBP1 and GBP2. These are large GTP-binding proteins of relative molecular mass 67,000 with a high-turnover GTPase activity and an antiviral effect. Here we have determined the crystal structure of full-length human GBP1 to 1.8 A resolution. The amino-terminal 278 residues constitute a modified G domain with a number of insertions compared to the canonical Ras structure, and the carboxy-terminal part is an extended helical domain with unique features. From the structure and biochemical experiments reported here, GBP1 appears to belong to the group of large GTP-binding proteins that includes Mx and dynamin, the common property of which is the ability to undergo oligomerization with a high concentration-dependent GTPase activity.
authors.affiliation: Max-Planck-Institut für Molekulare Physiologie, Dortmund, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Prakash
authors.forename: G J
authors.initials: GJ
authors.lastname: Praefcke
authors.forename: L
authors.initials: L
authors.lastname: Renault
authors.forename: A
authors.initials: A
authors.lastname: Wittinghofer
authors.forename: C
authors.initials: C
authors.lastname: Herrmann
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018360:Crystallography, X-Ray; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics; D034281:Dynamins; D004926:Escherichia coli; D020558:GTP Phosphohydrolases / Q000737:chemistry; D019204:GTP-Binding Proteins / Q000737:chemistry* / Q000235:genetics; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry; D017386:Sequence Homology, Amino Acid
chemical_list: D004268:DNA-Binding Proteins; C490287:GBP1 protein, human; D011994:Recombinant Proteins; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D034281:Dynamins