RGGT binds the RAB-binding subunit

Stable Identifier
R-HSA-8870465
Type
Reaction [binding]
Species
Homo sapiens
Compartment
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The catalytic dimer of RGGTA and B interacts with RAB-escorting proteins 1 or 2 (CHM and CHML, also known as REP-1 and REP-2) to form a functional trimeric RAB geranylgeranyl transferase complex that is capable of binding and geranylgeranylating newly synthesized RAB proteins (Baron and Seabra, 2008; reviewed in Leung et al, 2006; Gutkowska and Swiezewska, 2012). There are two models for the formation of a functional enzyme:substrate complex. In the classical model, unprenylated RAB first binds to REP and is subsequently presented to the catalytic subunits of the GGTase. Incorporation of geranylgeranyl pyrophosphate (GGPP) strengthens the interaction between enzyme and substrate (Andres et al, 1993; Thoma et al, 2001a). In the alternate route, which is depicted in this pathway, RGGTA and RGGTB first bind to REP in a GGPP-dependent manner in the absence of the RAB substrate. Unprenylated RABs then bind to the fully formed GGTase for geranylgeranylation (Thoma et al, 2001b; 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
22694141 Structure, regulation and cellular functions of Rab geranylgeranyl transferase and its cellular partner Rab Escort Protein

Gutkowska, M, Swiezewska, E

Mol. Membr. Biol. 2012
16401880 Thematic review series: lipid posttranslational modifications. geranylgeranylation of Rab GTPases

Leung, KF, Baron, R, Seabra, MC

J. Lipid Res. 2006
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
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