6D4G

N-GTPase domain of p190RhoGAP-A

Summary for 6D4G

• Entry DOI: 10.2210/pdb6d4g/pdb
• Related: 3c5h
• Descriptor: Rho GTPase-activating protein 35, GUANOSINE-5'-TRIPHOSPHATE, MAGNESIUM ION, ... (4 entities in total)
• Functional Keywords: gtpase, pseudogtpase, gtp, p190rhogap, hydrolase
• Biological source: Rattus norvegicus (Rat)
• Total number of polymer chains: 2
• Total formula weight: 62347.05

Authors

Stiegler, A.L.,Boggon, T.J. (deposition date: 2018-04-18, release date: 2018-09-12, Last modification date: 2023-10-04)

Primary citation

Stiegler, A.L.,Boggon, T.J.
The N-Terminal GTPase Domain of p190RhoGAP Proteins Is a PseudoGTPase.
Structure, 26:1451-, 2018

PubMed Abstract: The pseudoGTPases are a rapidly growing and important group of pseudoenzymes. p190RhoGAP proteins are critical regulators of Rho signaling and contain two previously identified pseudoGTPase domains. Here we report that p190RhoGAP proteins contain a third pseudoGTPase domain, termed N-GTPase. We find that GTP constitutively purifies with the N-GTPase domain, and a 2.8-Å crystal structure of p190RhoGAP-A co-purified with GTP reveals an unusual GTP-Mg binding pocket. Six inserts in N-GTPase indicate perturbed catalytic activity and inability to bind to canonical GTPase activating proteins, guanine nucleotide exchange factors, and effector proteins. Biochemical analysis shows that N-GTPase does not detectably hydrolyze GTP, and exchanges nucleotide only under harsh Mg chelation. Furthermore, mutational analysis shows that GTP and Mg binding stabilizes the domain. Therefore, our results support that N-GTPase is a nucleotide binding, non-hydrolyzing, pseudoGTPase domain that may act as a protein-protein interaction domain. Thus, unique among known proteins, p190RhoGAPs contain three pseudoGTPase domains.

PubMed: 30174148
DOI: 10.1016/j.str.2018.07.015

Experimental method

X-RAY DIFFRACTION (2.8 Å)