氟化物稳定GTP酶过渡态的不同机制的证据。
Evidence for distinct mechanisms of transition state stabilization of GTPases by fluoride.
作者信息
Vincent S, Brouns M, Hart M J, Settleman J
机构信息
Massachusetts General Hospital Cancer Center and Harvard Medical School, Building 149, 13th Street, Charlestown, MA 02129, USA.
出版信息
Proc Natl Acad Sci U S A. 1998 Mar 3;95(5):2210-5. doi: 10.1073/pnas.95.5.2210.
Abstract
GTPase-activating proteins (GAPs) function by stabilizing the GTPase transition state. This has been most clearly demonstrated by the formation of a high-affinity complex between various GAPs and GDP-bound GTPases in the presence of aluminum tetrafluoride, which can mimic the gamma-phosphate of GTP. Herein, we report that p190 RhoGAP forms a high-affinity complex with Rho GTPases in the presence of fluoride ions, suggesting that p190 also functions to stabilize the GTPase transition state. However, this Rho-p190 complex does not require aluminum ions or even guanine nucleotide, indicating a distinct role for fluoride that is not consistent with the gamma-phosphate-mimicking hypothesis. These results indicate that it is necessary to reconsider the assumed role of fluoride in stabilizing a variety of other GTPase-GAP interactions where the requirement for aluminum or guanine nucleotide has not yet been addressed.
摘要
GTP酶激活蛋白（GAPs）通过稳定GTP酶的过渡态发挥作用。在四氟化铝存在的情况下，各种GAPs与结合GDP的GTP酶之间形成高亲和力复合物，这一点得到了最清晰的证明，四氟化铝可以模拟GTP的γ-磷酸基团。在此，我们报告p190 RhoGAP在氟离子存在的情况下与Rho GTP酶形成高亲和力复合物，表明p190也起到稳定GTP酶过渡态的作用。然而，这种Rho - p190复合物不需要铝离子甚至鸟嘌呤核苷酸，这表明氟具有独特的作用，与γ-磷酸基团模拟假说不一致。这些结果表明，有必要重新考虑氟在稳定各种其他GTP酶 - GAP相互作用中所假定的作用，在这些相互作用中，铝或鸟嘌呤核苷酸的需求尚未得到研究。
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