4HL4

Crystal structure of the human TBC1D20 RabGAP domain

Summary for 4HL4

• Entry DOI: 10.2210/pdb4hl4/pdb
• Related: 4HLQ
• Descriptor: TBC1 domain family member 20, BERYLLIUM TRIFLUORIDE ION, ACETATE ION, ... (4 entities in total)
• Functional Keywords: tbc, rabgap, rab1b, hydrolase activator, catalytic domain, fluorides, gtpase-activating proteins, rab gtp-binding protein, gtp hydrolase
• Biological source: Homo sapiens (human)
• Cellular location: Membrane; Multi-pass membrane protein (Potential): Q96BZ9
• Total number of polymer chains: 1
• Total formula weight: 33873.82

Authors

Gazdag, E.M.,Gavriljuk, K.,Itzen, A.,Koetting, C.,Gerwert, K.,Goody, R.S. (deposition date: 2012-10-16, release date: 2013-01-16, Last modification date: 2024-03-20)

Primary citation

Gavriljuk, K.,Gazdag, E.M.,Itzen, A.,Kotting, C.,Goody, R.S.,Gerwert, K.
Catalytic mechanism of a mammalian Rab-RabGAP complex in atomic detail.
Proc.Natl.Acad.Sci.USA, 109:21348-21353, 2012

PubMed Abstract: 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.

PubMed: 23236136
DOI: 10.1073/pnas.1214431110

Experimental method

X-RAY DIFFRACTION (2.2 Å)