5IRC

p190A GAP domain complex with RhoA

Summary for 5IRC

• Entry DOI: 10.2210/pdb5irc/pdb
• Descriptor: Rho GTPase-activating protein 35, Transforming protein RhoA, CHLORIDE ION, ... (7 entities in total)
• Functional Keywords: protein-protein complex, transition state, gtpase, gap domain, protein binding
• Biological source: Rattus norvegicus (Rat); More
• Total number of polymer chains: 4
• Total formula weight: 89458.46

Authors

Derewenda, U.,Derewenda, Z. (deposition date: 2016-03-12, release date: 2016-08-17, Last modification date: 2025-04-02)

Primary citation

Amin, E.,Jaiswal, M.,Derewenda, U.,Reis, K.,Nouri, K.,Koessmeier, K.T.,Aspenstrom, P.,Somlyo, A.V.,Dvorsky, R.,Ahmadian, M.R.
Deciphering the Molecular and Functional Basis of RHOGAP Family Proteins: A SYSTEMATIC APPROACH TOWARD SELECTIVE INACTIVATION OF RHO FAMILY PROTEINS.
J.Biol.Chem., 291:20353-20371, 2016

PubMed Abstract: RHO GTPase-activating proteins (RHOGAPs) are one of the major classes of regulators of the RHO-related protein family that are crucial in many cellular processes, motility, contractility, growth, differentiation, and development. Using database searches, we extracted 66 distinct human RHOGAPs, from which 57 have a common catalytic domain capable of terminating RHO protein signaling by stimulating the slow intrinsic GTP hydrolysis (GTPase) reaction. The specificity of the majority of the members of RHOGAP family is largely uncharacterized. Here, we comprehensively investigated the sequence-structure-function relationship between RHOGAPs and RHO proteins by combining our in vitro data with in silico data. The activity of 14 representatives of the RHOGAP family toward 12 RHO family proteins was determined in real time. We identified and structurally verified hot spots in the interface between RHOGAPs and RHO proteins as critical determinants for binding and catalysis. We have found that the RHOGAP domain itself is nonselective and in some cases rather inefficient under cell-free conditions. Thus, we propose that other domains of RHOGAPs confer substrate specificity and fine-tune their catalytic efficiency in cells.

PubMed: 27481945
DOI: 10.1074/jbc.M116.736967

Experimental method

X-RAY DIFFRACTION (1.72 Å)