{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T03:15:41Z","timestamp":1766546141957,"version":"3.37.3"},"reference-count":52,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2016,3,9]],"date-time":"2016-03-09T00:00:00Z","timestamp":1457481600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health Grant","doi-asserted-by":"crossref","award":["GM0585187"],"award-info":[{"award-number":["GM0585187"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Proteins"],"published-print":{"date-parts":[[2016,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Intrinsically disordered proteins (IDPs) are often involved in signaling and regulatory functions, through binding to cellular targets. Many IDPs undergo disorder\u2010to\u2010order transitions upon binding. Both the binding mechanisms and the magnitudes of the binding rate constants can have functional importance. Previously we have found that the coupled binding and folding of any IDP generally follows a sequential mechanism that we term dock\u2010and\u2010coalesce, whereby one segment of the IDP first docks to its subsite on the target surface and the remaining segments subsequently coalesce around their respective subsites. Here we applied our TransComp method within the framework of the dock\u2010and\u2010coalesce mechanism to dissect the binding kinetics of two Rho\u2010family GTPases, Cdc42 and TC10, with two intrinsically disordered effectors, WASP and Pak1. TransComp calculations identified the basic regions preceding the GTPase binding domains (GBDs) of the effectors as the docking segment. For Cdc42 binding with both WASP and Pak1, the calculated docking rate constants are close to the observed overall binding rate constants, suggesting that basic\u2010region docking is the rate\u2010limiting step and subsequent conformational coalescence of the GBDs on the Cdc42 surface is fast. The possibility that conformational coalescence of the WASP GBD on the TC10 surface is slow warrants further experimental investigation. The account for the differences in binding rate constants among the three GTPase\u2010effector systems and mutational effects therein yields deep physical and mechanistic insight into the binding processes. Our approach may guide the selection of mutations that lead to redesigned binding pathways. Proteins 2016; 84:674\u2013685. \u00a9 2016 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/prot.25018","type":"journal-article","created":{"date-parts":[[2016,2,16]],"date-time":"2016-02-16T08:19:44Z","timestamp":1455610784000},"page":"674-685","source":"Crossref","is-referenced-by-count":18,"title":["Mechanism and rate constants of the Cdc42 GTPase binding with intrinsically disordered effectors"],"prefix":"10.1002","volume":"84","author":[{"given":"Xiaodong","family":"Pang","sequence":"first","affiliation":[{"name":"Department of Physics and Institute of Molecular Biophysics Florida State University Tallahassee Florida 32306"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huan\u2010Xiang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Physics and Institute of Molecular Biophysics Florida State University Tallahassee Florida 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