6d4g

Publication Abstract from PubMed

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-A crystal structure of p190RhoGAP-A co-purified with GTP reveals an unusual GTP-Mg(2+) 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(2+) chelation. Furthermore, mutational analysis shows that GTP and Mg(2+) 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.

The N-Terminal GTPase Domain of p190RhoGAP Proteins Is a PseudoGTPase.,Stiegler AL, Boggon TJ Structure. 2018 Aug 16. pii: S0969-2126(18)30261-2. doi:, 10.1016/j.str.2018.07.015. PMID:30174148^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.