The structure of the RLIP76 RhoGAP-Ral binding domain dyad: fixed position of the domains leads to dual engagement of small G proteins at the membrane.
The structure of the RLIP76 RhoGAP-Ral binding domain dyad: fixed position of the domains leads to dual engagement of small G proteins at the membrane.
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DOI：
10.1016/j.str.2013.09.007
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发表时间：
2013-12-03
期刊：
影响因子：
5.7
通讯作者：
Mott, Helen R.
中科院分区：
文献类型：
--
作者：
Rajasekar, Karthik V.;Campbell, Louise J.;Nietlispach, Daniel;Owen, Darerca;Mott, Helen R.
RLIP 76是Ral小GTP酶的效应子，Ral小GTP酶又位于主调节子Ras的下游。越来越多的证据表明Ral和RLIP 76在肿瘤发生、侵袭和转移中起作用。RLIP 76含有RhoGAP结构域和Ral结合结构域（GBD），因此是Ras和Rho家族信号传导之间的节点。RhoGAP-GBD二联体的结构揭示了RLIP 76 RhoGAP结构域采用典型的RhoGAP结构域结构，并且两个RLIP 76结构域之间的接头是结构化的，固定了两个结构域的取向并允许RLIP 76同时与Rho家族GTP酶和Ral相互作用。然而，并置的结构域在功能上不相互影响，这表明RLIP 76-Ral相互作用控制细胞定位，并且两个结构域的固定取向使RhoGAP结构域相对于膜取向，使其能够完美地准备好接合其靶G蛋白。RLIP 76的RhoGAP-Ral结合结构域二联体的结构已得到解决。结构域间连接体接触两个结构域并固定它们的方向RhoGAP结构域是Cdc 42和Rac 1的弱GAP，Ral和Rho家族蛋白可以同时与RLIP 76相互作用。Rajasekar等人解决了一个结构，并揭示了两个结构域之间的连接器是结构化的，固定了它们的方向。这种定向使它们能够与目标G蛋白结合。
RLIP76 is an effector for Ral small GTPases, which in turn lie downstream of the master regulator Ras. Evidence is growing that Ral and RLIP76 play a role in tumorigenesis, invasion, and metastasis. RLIP76 contains both a RhoGAP domain and a Ral binding domain (GBD) and is, therefore, a node between Ras and Rho family signaling. The structure of the RhoGAP-GBD dyad reveals that the RLIP76 RhoGAP domain adopts a canonical RhoGAP domain structure and that the linker between the two RLIP76 domains is structured, fixing the orientation of the two domains and allowing RLIP76 to interact with Rho-family GTPases and Ral simultaneously. However, the juxtaposed domains do not influence each other functionally, suggesting that the RLIP76-Ral interaction controls cellular localization and that the fixed orientation of the two domains orientates the RhoGAP domain with respect to the membrane, allowing it to be perfectly poised to engage its target G proteins. The structure of the RLIP76 RhoGAP-Ral binding domain dyad has been solved The interdomain linker contacts both domains and fixes their orientation The RhoGAP domain is a poor GAP for Cdc42 and Rac1 in vitro Ral and Rho family proteins can interact simultaneously with RLIP76 RLIP76 is an effector for Ral small GTPases that contains a RhoGAP domain adjacent to a Ral-binding domain. Rajasekar et al. solve a structure and reveal that the linker between the two domains is structured, fixing their orientation. This orientation allows them to engage their target G proteins.
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DOI：
10.1016/j.str.2010.05.013
发表时间：
2010-08-11
期刊：
Structure (London, England : 1993)
影响因子：
--
作者：
Fenwick RB;Campbell LJ;Rajasekar K;Prasannan S;Nietlispach D;Camonis J;Owen D;Mott HR
通讯作者：
Mott HR
影响因子：
4.8
作者：
JULLIENFLORES, V;DORSEUIL, O;CAMONIS, JH
通讯作者：
CAMONIS, JH
DOI：
10.1107/s0907444998003254
发表时间：
1998-09-01
期刊：
ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
影响因子：
--
作者：
Brunger, AT;Adams, PD;Warren, GL
通讯作者：
Warren, GL
影响因子：
5.3
作者：
Lim, Kian-Huat;Brady, Donita C.;Counter, Christopher M.
通讯作者：
Counter, Christopher M.
影响因子：
10.5
作者：
Hamad, NM;Elconin, JH;Counter, CM
通讯作者：
Counter, CM