The centaurin {gamma}-1 GTPase-like domain functions as an NTPase

Meera Soundararajan , Xiaowen Yang , Jonathan M Elkins , Frank Sobott , Declan A Doyle (1)

1 Structural Genomics Consortium

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 PI-3 kinase, a key regulator of cell proliferation, motility and vesicular trafficking. In this report, through X-ray structural analysis, enzymatic assays and nucleotide binding studies, we show that for centaurin gamma-1 (CENTG1) the GTPase-like domain has broader tri-nucleotide 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.

Mots clés: Life Sciences

Meera Soundararajan, Xiaowen Yang, Jonathan M Elkins, Frank Sobott, Declan A Doyle. The centaurin {gamma}-1 GTPase-like domain functions as an NTPase. Biochemical Journal, 2006, 401 (3), pp.679-688. ⟨10.1042/BJ20060555⟩. ⟨hal-00478577⟩