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Title: p190RhoGAP proteins contain pseudoGTPase domains

Abstract

The two p190RhoGAP proteins, p190RhoGAP-A and -B, are key regulators of Rho GTPase signaling and are essential for actin cytoskeletal structure and contractility. Here we report the discovery of two evolutionarily conserved GTPase-like domains located in the ‘middle domain’, previously thought to be unstructured. Deletion of these domains reduces RhoGAP activity. Crystal structures, MANT-GTPγS binding, thermal denaturation, biochemical assays and sequence homology analysis all strongly support defects in nucleotide-binding activity. Analysis of p190RhoGAP proteins therefore indicates the presence of two previously unidentified domains which represent an emerging group of pseudoenzymes, the pseudoGTPases.

Authors:
 [1];  [1]
  1. Yale Univ. School of Medicine, New Haven, CT (United States)
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES). Scientific User Facilities Division; National Inst. of Health
OSTI Identifier:
1430346
Grant/Contract Number:  
AC02-06CH11357; P41GM103403; R01NS085078; R01GM109487; R01GM114621; R01GM102262; R01GM100411; P50CA121974; S10OD018007
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
Nature Communications
Additional Journal Information:
Journal Volume: 8; Journal Issue: 1; Journal ID: ISSN 2041-1723
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES; Hydrolases; Proteins; X-ray crystallography

Citation Formats

Stiegler, Amy L., and Boggon, Titus J. p190RhoGAP proteins contain pseudoGTPase domains. United States: N. p., 2017. Web. doi:10.1038/s41467-017-00483-x.
Stiegler, Amy L., & Boggon, Titus J. p190RhoGAP proteins contain pseudoGTPase domains. United States. https://doi.org/10.1038/s41467-017-00483-x
Stiegler, Amy L., and Boggon, Titus J. Mon . "p190RhoGAP proteins contain pseudoGTPase domains". United States. https://doi.org/10.1038/s41467-017-00483-x. https://www.osti.gov/servlets/purl/1430346.
@article{osti_1430346,
title = {p190RhoGAP proteins contain pseudoGTPase domains},
author = {Stiegler, Amy L. and Boggon, Titus J.},
abstractNote = {The two p190RhoGAP proteins, p190RhoGAP-A and -B, are key regulators of Rho GTPase signaling and are essential for actin cytoskeletal structure and contractility. Here we report the discovery of two evolutionarily conserved GTPase-like domains located in the ‘middle domain’, previously thought to be unstructured. Deletion of these domains reduces RhoGAP activity. Crystal structures, MANT-GTPγS binding, thermal denaturation, biochemical assays and sequence homology analysis all strongly support defects in nucleotide-binding activity. Analysis of p190RhoGAP proteins therefore indicates the presence of two previously unidentified domains which represent an emerging group of pseudoenzymes, the pseudoGTPases.},
doi = {10.1038/s41467-017-00483-x},
url = {https://www.osti.gov/biblio/1430346}, journal = {Nature Communications},
issn = {2041-1723},
number = 1,
volume = 8,
place = {United States},
year = {2017},
month = {9}
}

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Cited by: 10 works
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    Works referencing / citing this record:

    X-Ray Diffraction data from p190RhoGAP pseudoGTPase, source of 5U4V structure
    dataset, January 2017


    Synchrotron Big Data Science
    journal, September 2018


    PseudoGTPase domains in p190RhoGAP proteins: a mini-review
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    Crystal structures of p120RasGAP N-terminal SH2 domain in its apo form and in complex with a p190RhoGAP phosphotyrosine peptide
    journal, December 2019