3DSS: Crystal Structure Of Rabggtase(delta Lrr; Delta Ig)

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.
PDB ID: 3DSSDownload
MMDB ID: 66633
PDB Deposition Date: 2008/7/14
Updated in MMDB: 2012/10
Experimental Method:
x-ray diffraction
Resolution: 1.8  Å
Source Organism:
Similar Structures:
Biological Unit for 3DSS: dimeric; determined by author and by software (PISA)
Molecular Components in 3DSS
Label Count Molecule
Proteins (2 molecules)
Geranylgeranyl Transferase Type-2 Subunit Alpha(Gene symbol: Rabggta)
Molecule annotation
Geranylgeranyl Transferase Type-2 Subunit Beta(Gene symbol: Rabggtb)
Molecule annotation
Chemicals (3 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB