Reactome | RGGT:CHM binds RABs

RGGT:CHM binds RABs

Stable Identifier

R-HSA-8870466

Type

Reaction [binding]

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

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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
8662963	Nucleotide dependence of Rab geranylgeranylation. Rab escort protein interacts preferentially with GDP-bound Rab Seabra, MC	J. Biol. Chem.	1996
8513495	cDNA cloning of component A of Rab geranylgeranyl transferase and demonstration of its role as a Rab escort protein Cremers, FP, Seabra, MC, Armstrong, SA, Andres, DA, Smeland, TE, Goldstein, JL, Brown, MS	Cell	1993
18532927	Rab geranylgeranylation occurs preferentially via the pre-formed REP-RGGT complex and is regulated by geranylgeranyl pyrophosphate Seabra, MC, Baron, RA	Biochem. J.	2008
11675392	Phosphoisoprenoids modulate association of Rab geranylgeranyltransferase with REP-1 Iakovenko, A, Goody, RS, Thomä, NH, Alexandrov, K	J. Biol. Chem.	2001
11141079	Allosteric regulation of substrate binding and product release in geranylgeranyltransferase type II Alexandrov, K, Iakovenko, A, Waldmann, H, Thomä, NH, Kalinin, A, Goody, RS	Biochemistry	2001
8631982	Mechanism of digeranylgeranylation of Rab proteins. Formation of a complex between monogeranylgeranyl-Rab and Rab escort protein Seabra, MC, Shen, F	J. Biol. Chem.	1996
7957092	Rab escort protein-1 is a multifunctional protein that accompanies newly prenylated rab proteins to their target membranes Seabra, MC, Steele-Mortimer, O, Horiuchi, H, Alexandrov, K, Zerial, M	EMBO J.	1994