RGGT:CHM binds RABs
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CHM and CHML are the substrate-binding subunits of the RAB geranylgeranyltransferase (GGTase) complex. CHMs, also known as RAB escort proteins (REPs) bind to unprenylated RAB proteins in the GDP bound state (Seabra, 1996). In the classical model of RAB recruitment, CHM proteins first bind the unprenylated RAB alone and then present it to the catalytic dimer of the RAB GGTase, while in the alternative model, depicted here, RAB recruitment occurs after the GGPP-dependent formation of a highly stable trimeric GGTase complex (Andres et al, 1993; Thoma et al, 2001a; Thoma et al 2001b; Baron and Seabra, 2008). After geranylgeranylation, binding of additional GGPP to the GGTase promotes release of the CHM:RAB complex, possibly through an allosteric mechanism (Baron and Seabra, 2008). CHM proteins remain in complex with the RABs after geranylgeranylation, dissociating after the RAB has been transferred to the target membrane (Alexandrov et al, 1994; Shen and Seabra, 1996; Baron and Seabra, 2008).
CHM和CHML是RAB香叶基香叶基转移酶(GGTase)复合物的底物结合亚基。CHM蛋白,亦称RAB伴随蛋白(REPs),在GDP结合状态下与未预烯化的RAB蛋白结合(Seabra, 1996)。在RAB招募的经典模型中,CHM蛋白首先与未预烯化的RAB蛋白结合,并将其呈递给RAB GGTase的催化二聚体;而在本图所描述的替代模型中,RAB招募发生在GGPP依赖性高度稳定的三角GGTase复合体形成之后(Andres et al, 1993; Thoma et al, 2001a; Thoma et al 2001b; Baron and Seabra, 2008)。在香叶基香叶基化之后,额外的GGPP结合到GGTase上促进CHM:RAB复合物的释放,可能通过变构机制(Baron and Seabra, 2008)。香叶基香叶基化后,CHM蛋白仍与RAB蛋白复合,在RAB蛋白被转移至靶膜后发生解离(Alexandrov et al, 1994; Shen and Seabra, 1996; Baron and Seabra, 2008)。
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