Soundararajan Meera, Yang Xiaowen, Elkins Jonathan M, Sobott Frank, Doyle Declan A
The Structural Genomics Consortium, University of Oxford, Botnar Research Centre, Oxford OX3 7LD, UK.
Biochem J. 2007 Feb 1;401(3):679-88. doi: 10.1042/BJ20060555.
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.
Centaurin蛋白家族包含具有GTP酶激活蛋白结构域的蛋白质，其中γ家族成员还含有一个类似GTP酶的结构域。Centaurin蛋白主要位于细胞核中，已知其可激活磷酸肌醇3激酶，这是细胞增殖、运动和囊泡运输的关键调节因子。在本研究中，通过X射线结构分析、酶活性测定和核苷酸结合研究，我们发现，对于CENTG1（centaurinγ-1）而言，其类似GTP酶的结构域具有更广泛的三核苷酸特异性。CENTG1的G4基序中，从典型GTP酶中高度保守的NKXD变为TQDR，导致特异性丧失、对核苷酸的亲和力降低以及更高的周转率。这些结果表明，centaurin蛋白可更准确地归类为NTP酶，并指出了细胞信号控制的替代机制。
