5cjp | pdb_00005cjp
The Structural Basis for Cdc42-Induced Dimerization of IQGAPs
Structural highlights
FunctionCDC42_HUMAN Plasma membrane-associated small GTPase which cycles between an active GTP-bound and an inactive GDP-bound state. In active state binds to a variety of effector proteins to regulate cellular responses. Involved in epithelial cell polarization processes. Regulates the bipolar attachment of spindle microtubules to kinetochores before chromosome congression in metaphase. Plays a role in the extension and maintenance of the formation of thin, actin-rich surface projections called filopodia. Mediates CDC42-dependent cell migration.[1] [2] [3] Publication Abstract from PubMedIn signaling, Rho-family GTPases bind effector proteins and alter their behavior. Here we present the crystal structure of Cdc42.GTP bound to the GTPase-activating protein (GAP)-related domain (GRD) of IQGAP2. Four molecules of Cdc42 are bound to two GRD molecules, which bind each other in a parallel dimer. Two Cdc42s bind very similarly to the Ras/RasGAP interaction, while the other two bind primarily to "extra domain" sequences from both GRDs, tying the GRDs together. Calorimetry confirms two-site binding of Cdc42.GTP for the GRDs of both IQGAP2 and IQGAP1. Mutation of important extra domain residues reduces binding to single-site and abrogates Cdc42 binding to a much larger IQGAP1 fragment. Importantly, Rac1.GTP displays only single-site binding to the GRDs, indicating that only Cdc42 promotes IQGAP dimerization. The structure identifies an unexpected role for Cdc42 in protein dimerization, thus expanding the repertoire of interactions of Ras family proteins with their targets. The Structural Basis for Cdc42-Induced Dimerization of IQGAPs.,LeCour L Jr, Boyapati VK, Liu J, Li Z, Sacks DB, Worthylake DK Structure. 2016 Sep 6;24(9):1499-1508. doi: 10.1016/j.str.2016.06.016. Epub 2016 , Aug 11. PMID:27524202[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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