RGGT:CHM binds RABs

Stable Identifier
R-HSA-8870466
Type
Reaction
Species
Homo sapiens
Compartment
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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).

Literature References
PubMed ID Title Journal Year
8513495 cDNA cloning of component A of Rab geranylgeranyl transferase and demonstration of its role as a Rab escort protein

Andres, DA, Seabra, MC, Brown, MS, Armstrong, SA, Smeland, TE, Cremers, FP, Goldstein, JL

Cell 1993
8662963 Nucleotide dependence of Rab geranylgeranylation. Rab escort protein interacts preferentially with GDP-bound Rab

Seabra, MC

J. Biol. Chem. 1996
18532927 Rab geranylgeranylation occurs preferentially via the pre-formed REP-RGGT complex and is regulated by geranylgeranyl pyrophosphate

Baron, RA, Seabra, MC

Biochem. J. 2008
11675392 Phosphoisoprenoids modulate association of Rab geranylgeranyltransferase with REP-1

Thomä, NH, Iakovenko, A, Goody, RS, Alexandrov, K

J. Biol. Chem. 2001
11141079 Allosteric regulation of substrate binding and product release in geranylgeranyltransferase type II

Thomä, NH, Iakovenko, A, Kalinin, A, Waldmann, H, Goody, RS, Alexandrov, K

Biochemistry 2001
8631982 Mechanism of digeranylgeranylation of Rab proteins. Formation of a complex between monogeranylgeranyl-Rab and Rab escort protein

Shen, F, Seabra, MC

J. Biol. Chem. 1996
7957092 Rab escort protein-1 is a multifunctional protein that accompanies newly prenylated rab proteins to their target membranes

Alexandrov, K, Horiuchi, H, Steele-Mortimer, O, Seabra, MC, Zerial, M

EMBO J. 1994
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