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首页> 外文期刊>Biochemistry >Novel activity of RGS14 on Go alpha and Gi alpha nucleotide binding and hydrolysis distinct from its RGS domain and GDI activity
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Novel activity of RGS14 on Go alpha and Gi alpha nucleotide binding and hydrolysis distinct from its RGS domain and GDI activity

机译：RGS14对Goα和Giα的新型活性与其RGS结构域和GDI活性不同的α和GIα核苷酸结合和水解

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摘要

The bifunctional protein RGS14 is both a GTPase activating protein (GAP) for Gi alpha and Go alpha and a guanine nucleotide dissociation inhibitor (GDI) for Gi alpha. This GDI activity is isolated to a region of the protein distinct from the RGS domain that contains an additional G protein-binding domain (RBD/GL). Here, we report that RGS14 missing its RGS domain (R14-RBD/GL) binds directly to Go and Gi to modulate nucleotide binding and hydrolysis by mechanisms distinct from its defined GDI activity. In brain pull-down assays, full-length RGS14 and R14-RBD/GL (but not the isolated RGS domain of RGS14) bind Go alpha-GDP, Gi alpha-GDP, and also G beta gamma. When reconstituted with M2 muscarinic receptors (M2) plus either Gi or Go, RGS4 (which has no RBD/GL domain) and full-length RGS 14 each markedly stimulates the steady-state GTPase activities of both G proteins, whereas R14-RBD/GL has little or no effect. R14-RBD/GL potentiates RGS4 GAP activity in membrane-based assays by increasing the apparent affinity of RGS4 for Gi alpha and Go alpha, suggesting a cooperative interaction between the RBD/GL domain, RGS4, and G alpha. This activity of R14-RBD/GL on RGS4 is not apparent in single-turnover solution GAP assays with purified Gi alpha or Go alpha, suggesting that membranes and/or receptors are required for this activity. When these findings are taken together, they indicate that regions of RGS14 outside of the RGS domain can bind inactive forms of Go and Gi to confer previously unappreciated activities that influence G alpha nucleotide binding and/or hydrolysis by mechanisms distinct from its RGS domain and established GDI activity.
机译：双官能蛋白RGS14是GIα的GTP酶活性蛋白（间隙），用于GIα和GOα和鸟嘌呤核苷酸解离抑制剂（GDI）。该GDI活性与含有另外的G蛋白结合结构域（RBD / G1）不同的蛋白质的蛋白质的区域。在这里，我们报告RGS14缺少其RGS域（R14-RBD / GL）直接结合，通过不同于其定义的GDI活性的机制调节核苷酸结合和水解。在脑下拉测定中，全长RGS14和R14-RBD / GL（但不是RGS14的分离的RGS结构域）结合α-GDP，GIα-GDP和Gβγ。当用M2毒蕈碱受体（M2）加上GI或GO，RGS4（没有RBD / GL结构域）和全长RGS 14，每个RGS 14都明显刺激了G蛋白的稳态GTP酶活性，而R14-RBD / GL几乎没有任何影响。 R14-RBD / GL通过增加RGS4对于GIα和GOα的表观亲和力来增强RGS4间隙活性，表明RBD / GL结构域，RGS4和Gα之间的协同相互作用。 RGS4上的R14-RBD / GL的这种活性在单周转溶液间隙测定中不明显，所述单片溶液间隙测定与纯化的GIα或αα，表明该活性需要膜和/或受体。当这些发现被占用时，它们表明RGS结构域之外的RGS14的区域可以结合无活性形式的GO和GI，以赋予通过与其RGS结构域不同的机制影响Gα核苷酸结合和/或水解的预先覆盖的活性，并建立GDI活动。

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