RhoGDI facilitates geranylgeranyltransferase-I-mediated RhoA prenylation.
RhoGDI facilitates geranylgeranyltransferase-I-mediated RhoA prenylation.
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RhoGDI 促进香叶基香叶基转移酶-I 介导的 RhoA 异戊二烯化。
DOI：
10.1016/j.bbrc.2014.09.024
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发表时间：
2014
影响因子：
3.1
通讯作者：
K. Alexandrov
中科院分区：
文献类型：
--
作者：
Z. Tnimov;D. Abankwa;K. Alexandrov
蛋白质异戊二烯化是一种翻译后修饰，其中法尼基或香叶基香叶基基团通过酶促连接到 C 末端半胱氨酸残基上。这种修饰对于小细胞 GTP 酶的活性至关重要，因为它允许它们与细胞内膜结合。从膜上解离出来的异戊二烯化蛋白质需要通过蛋白质载体运输通过水性细胞质，从而保护疏水性锚不受溶剂的影响。其中一种载体是 Rho GDP 解离抑制剂 (RhoGDI)。最近，研究表明，与 RhoGDI 无关的异戊二烯化 Rho 蛋白会在细胞中进行蛋白水解。我们假设 RhoGDI 的作用可能不仅是与异戊烯化蛋白相关，而且还调节细胞中的异戊二烯化过程。这一想法得到了以下事实的支持：RhoGDI 在体外以高亲和力结合未异戊二烯化和异戊二烯化的 Rho 蛋白，因此，这些相互作用可能会影响异戊二烯化的动力学。我们通过实验解决了这个问题，发现 RhoGDI 提高了香叶基香叶基转移酶-I 在 RhoA 异戊二烯化中的催化效率。然而，我们没有观察到三元 RhoGDI*RhoA*GGTase-I 复合物的形成，表明香叶基香叶基转移酶-I 和 RhoGDI 的顺序操作。我们的结果表明，RhoGDI 通过动力学捕获反应产物来加速 Rho 异戊二烯化，从而提高产物释放速率。
Protein prenylation is a post-translational modification where farnesyl or geranylgeranyl groups are enzymatically attached to a C-terminal cysteine residue. This modification is essential for the activity of small cellular GTPases, as it allows them to associate with intracellular membranes. Dissociated from membranes, prenylated proteins need to be transported through the aqueous cytoplasm by protein carriers that shield the hydrophobic anchor from the solvent. One such carrier is Rho GDP dissociation inhibitor (RhoGDI). Recently, it was shown that prenylated Rho proteins that are not associated with RhoGDI are subjected to proteolysis in the cell. We hypothesized that the role of RhoGDI might be not only to associate with prenylated proteins but also to regulate the prenylation process in the cell. This idea is supported by the fact that RhoGDI binds both unprenylated and prenylated Rho proteins with high affinityin vitro, and hence, these interactions may affect the kinetics of prenylation. We addressed this question experimentally and found that RhoGDI increased the catalytic efficiency of geranylgeranyl transferase-I in RhoA prenylation. Nevertheless, we did not observe formation of a ternary RhoGDI∗RhoA∗GGTase-I complex, indicating sequential operation of geranylgeranyltransferase-I and RhoGDI. Our results suggest that RhoGDI accelerates Rho prenylation by kinetically trapping the reaction product, thereby increasing the rate of product release.
哺乳动物蛋白香叶基香叶基转移酶-I：底物特异性、动力学机制、金属要求和亲和标记。
影响因子：
2.9
作者：
Yokoyama,K;McGeady,P;Gelb,MH
通讯作者：
Gelb,MH
影响因子：
2.9
作者：
Kuzmic, P
通讯作者：
Kuzmic, P
影响因子：
5.6
作者：
Reid, TS;Terry, KL;Beese, LS
通讯作者：
Beese, LS