1kzg
DbsCdc42(Y889F)
Structural highlights
FunctionMCF2L_MOUSE Guanine nucleotide exchange factor that potentially links pathways that signal through RAC1, RHOA and CDC42. Catalyzes guanine nucleotide exchange on RHOA and CDC42 and interacts specifically with the GTP-bound form of RAC1, suggesting that it functions as an effector of RAC1. May also participate in axonal transport in the brain. Becomes activated and highly tumorigenic by truncation of the N-terminus (By similarity). Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedDbl-related oncoproteins are guanine nucleotide exchange factors (GEFs) specific for Rho guanosine triphosphatases (GTPases) and invariably possess tandem Dbl (DH) and pleckstrin homology (PH) domains. While it is known that the DH domain is the principal catalytic subunit, recent biochemical data indicate that for some Dbl-family proteins, such as Dbs and Trio, PH domains may cooperate with their associated DH domains in promoting guanine nucleotide exchange of Rho GTPases. In order to gain an understanding of the involvement of these PH domains in guanine nucleotide exchange, we have determined the crystal structure of a DH/PH fragment from Dbs in complex with Cdc42. The complex features the PH domain in a unique conformation distinct from the PH domains in the related structures of Sos1 and Tiam1.Rac1. Consequently, the Dbs PH domain participates with the DH domain in binding Cdc42, primarily through a set of interactions involving switch 2 of the GTPase. Comparative sequence analysis suggests that a subset of Dbl-family proteins will utilize their PH domains similarly to Dbs. A crystallographic view of interactions between Dbs and Cdc42: PH domain-assisted guanine nucleotide exchange.,Rossman KL, Worthylake DK, Snyder JT, Siderovski DP, Campbell SL, Sondek J EMBO J. 2002 Mar 15;21(6):1315-26. PMID:11889037[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
| ||||||||||||||||||
