Structural highlights
3dst is a 2 chain structure with sequence from Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Ligands: | , , |
| Related: | 3c72, 3dss, 3dsu, 3dsv, 3dsw, 3dsx |
| Gene: | Rabggta, Ggta (Rattus norvegicus), Rabggtb, Ggtb (Rattus norvegicus) |
| Activity: | Protein geranylgeranyltransferase type II, with EC number 2.5.1.60 |
| Resources: | FirstGlance, OCA, RCSB, PDBsum |
Function
[PGTA_RAT] Catalyzes the transfer of a geranyl-geranyl moiety from geranyl-geranyl pyrophosphate to both cysteines in Rab proteins with an -XXCC, -XCXC and -CCXX C-terminal, such as RAB1A, RAB3A and RAB5A respectively. [PGTB2_RAT] Catalyzes the transfer of a geranyl-geranyl moiety from geranyl-geranyl pyrophosphate to both cysteines in Rab proteins with an -XXCC, -XCXC and -CCXX C-terminal, such as RAB1A, RAB3A and RAB5A respectively.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Post-translational isoprenylation of proteins is carried out by three related enzymes: farnesyltransferase, geranylgeranyl transferase-I, and Rab geranylgeranyl transferase (RabGGTase). Despite the fact that the last one is responsible for the largest number of individual protein prenylation events in the cell, no structural information is available on its interaction with substrates and products. Here, we present structural and biophysical analyses of RabGGTase in complex with phosphoisoprenoids as well as with the prenylated peptides that mimic the C terminus of Rab7 GTPase. The data demonstrate that, unlike other protein prenyl transferases, both RabGGTase and its substrate RabGTPases completely 'outsource' their specificity for each other to an accessory subunit, the Rab escort protein (REP). REP mediates the placement of the C terminus of RabGTPase into the active site of RabGGTase through a series protein-protein interactions of decreasing strength and selectivity. This arrangement enables RabGGTase to prenylate any cysteine-containing sequence. On the basis of our structural and thermodynamic data, we propose that RabGGTase has evolved from a GGTase-I-like molecule that 'learned' to interact with a recycling factor (GDI) that, in turn, eventually gave rise to REP.
Structures of RabGGTase-substrate/product complexes provide insights into the evolution of protein prenylation.,Guo Z, Wu YW, Das D, Delon C, Cramer J, Yu S, Thuns S, Lupilova N, Waldmann H, Brunsveld L, Goody RS, Alexandrov K, Blankenfeldt W EMBO J. 2008 Sep 17;27(18):2444-56. Epub 2008 Aug 28. PMID:18756270[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Guo Z, Wu YW, Das D, Delon C, Cramer J, Yu S, Thuns S, Lupilova N, Waldmann H, Brunsveld L, Goody RS, Alexandrov K, Blankenfeldt W. Structures of RabGGTase-substrate/product complexes provide insights into the evolution of protein prenylation. EMBO J. 2008 Sep 17;27(18):2444-56. Epub 2008 Aug 28. PMID:18756270 doi:10.1038/emboj.2008.164
