Structural highlights
4hlq is a 10 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
|
| Ligands: | , , , |
| Related: | 4hl4 |
| Gene: | TBC1D20, C20orf140 (HUMAN), RAB1B (HUMAN) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Disease
[TBC20_HUMAN] Micro syndrome. The disease is caused by mutations affecting the gene represented in this entry.
Function
[TBC20_HUMAN] GTPase-activating protein specific for Rab1 and Rab2 small GTPase families for which it can accelerate the intrinsic GTP hydrolysis rate by more than five orders of magnitude. [RAB1B_HUMAN] Protein transport. Regulates vesicular transport between the endoplasmic reticulum and successive Golgi compartments.[1]
Publication Abstract from PubMed
Rab GTPases, key regulators of vesicular transport, hydrolyze GTP very slowly unless assisted by Rab GTPase-activating proteins (RabGAPs). Dysfunction of RabGAPs is involved in many diseases. By combining X-ray structure analysis and time-resolved FTIR spectroscopy we reveal here the detailed molecular reaction mechanism of a complex between human Rab and RabGAP at the highest possible spatiotemporal resolution and in atomic detail. A glutamine residue of Rab proteins (cis-glutamine) that is essential for intrinsic activity is less important in the GAP-activated reaction. During generation of the RabGAP.Rab:GTP complex, there is a rapid conformational change in which the cis-glutamine is replaced by a glutamine from RabGAP (trans-glutamine); this differs from the RasGAP mechanism, where the cis-glutamine is also important for GAP catalysis. However, as in the case of Ras, a trans-arginine is also recruited to complete the active center during this conformational change. In contrast to the RasGAP mechanism, an accumulation of a state in which phosphate is bound is not observed, and bond breakage is the rate-limiting step. The movement of trans-glutamine and trans-arginine into the catalytic site and bond breakage during hydrolysis are monitored in real time. The combination of X-ray structure analysis and time-resolved FTIR spectroscopy provides detailed insight in the catalysis of human Rab GTPases.
Catalytic mechanism of a mammalian Rab{middle dot}RabGAP complex in atomic detail.,Gavriljuk K, Gazdag EM, Itzen A, Kotting C, Goody RS, Gerwert K Proc Natl Acad Sci U S A. 2012 Dec 26;109(52):21348-53. doi:, 10.1073/pnas.1214431110. Epub 2012 Dec 12. PMID:23236136[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Overmeyer JH, Wilson AL, Erdman RA, Maltese WA. The putative "switch 2" domain of the Ras-related GTPase, Rab1B, plays an essential role in the interaction with Rab escort protein. Mol Biol Cell. 1998 Jan;9(1):223-35. PMID:9437002
- ↑ Gavriljuk K, Gazdag EM, Itzen A, Kotting C, Goody RS, Gerwert K. Catalytic mechanism of a mammalian Rab{middle dot}RabGAP complex in atomic detail. Proc Natl Acad Sci U S A. 2012 Dec 26;109(52):21348-53. doi:, 10.1073/pnas.1214431110. Epub 2012 Dec 12. PMID:23236136 doi:http://dx.doi.org/10.1073/pnas.1214431110
