title: The centaurin gamma-1 GTPase-like domain functions as an NTPase.
abstract: Centaurins are a family of proteins that contain GTPase-activating protein domains, with the gamma family members containing in addition a GTPase-like domain. Centaurins reside mainly in the nucleus and are known to activate phosphoinositide 3-kinase, a key regulator of cell proliferation, motility and vesicular trafficking. In the present study, using X-ray structural analysis, enzymatic assays and nucleotide-binding studies, we show that, for CENTG1 (centaurin gamma-1) the GTPase-like domain has broader trinucleotide specificity. Alterations within the G4 motif of CENTG1 from the highly conserved NKXD found in typical GTPases to TQDR result in the loss of specificity, a lower affinity for the nucleotides and higher turnover rates. These results indicate that the centaurins could be more accurately classified as NTPases and point to alternative mechanisms of cell signalling control.
authors.affiliation: The Structural Genomics Consortium, University of Oxford, Botnar Research Centre, Oxford OX3 7LD, UK.
authors.forename: Meera
authors.initials: M
authors.lastname: Soundararajan
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Yang
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Elkins
authors.forename: Frank
authors.initials: F
authors.lastname: Sobott
authors.forename: Declan A
authors.initials: DA
authors.lastname: Doyle
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D003001:Cloning, Molecular; D004926:Escherichia coli / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D020690:GTPase-Activating Proteins / Q000737:chemistry* / Q000378:metabolism*; D006868:Hydrolysis; D008958:Models, Molecular; D015394:Molecular Structure; D043583:Nucleoside-Triphosphatase / Q000737:chemistry / Q000378:metabolism*; D009711:Nucleotides / Q000378:metabolism; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D013379:Substrate Specificity; D018631:ras Proteins / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D020690:GTPase-Activating Proteins; D009711:Nucleotides; C485997:AGAP2 protein, human; D019204:GTP-Binding Proteins; D043583:Nucleoside-Triphosphatase; D018631:ras Proteins