{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T13:11:44Z","timestamp":1773493904239,"version":"3.50.1"},"reference-count":50,"publisher":"Wiley","issue":"20","license":[{"start":{"date-parts":[[2017,8,30]],"date-time":"2017-08-30T00:00:00Z","timestamp":1504051200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["GM058187"],"award-info":[{"award-number":["GM058187"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["GM118091"],"award-info":[{"award-number":["GM118091"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FEBS Journal"],"published-print":{"date-parts":[[2017,10]]},"abstract":"<jats:p>Intrinsically disordered proteins (<jats:styled-content style=\"fixed-case\">IDP<\/jats:styled-content>s) play key roles in signaling and regulation. Many <jats:styled-content style=\"fixed-case\">IDP<\/jats:styled-content>s undergo folding upon binding to their targets. We have proposed that coupled folding and binding of <jats:styled-content style=\"fixed-case\">IDP<\/jats:styled-content>s generally follow a dock\u2010and\u2010coalesce mechanism, whereby a segment of the <jats:styled-content style=\"fixed-case\">IDP<\/jats:styled-content>, through diffusion, docks to its cognate subsite and, subsequently, the remaining segments coalesce around their subsites. Here, by a combination of experiment and computation, we determined the precise form of dock\u2010and\u2010coalesce operating in the association between the intrinsically disordered <jats:styled-content style=\"fixed-case\">GTP<\/jats:styled-content>ase\u2010binding domain (<jats:styled-content style=\"fixed-case\">GBD<\/jats:styled-content>) of the Wiskott\u2013Aldrich Syndrome protein and the Cdc42 <jats:styled-content style=\"fixed-case\">GTP<\/jats:styled-content>ase. The association rate constants (<jats:italic>k<\/jats:italic><jats:sub>a<\/jats:sub>) were measured by stopped\u2010flow fluorescence under various solvent conditions. <jats:italic>k<\/jats:italic><jats:sub>a<\/jats:sub> reached 10<jats:sup>7<\/jats:sup> <jats:sc>m<\/jats:sc><jats:sup>\u22121<\/jats:sup>\u00b7s<jats:sup>\u22121<\/jats:sup> at physiological ionic strength and had a strong salt dependence, suggesting that an electrostatically enhanced, diffusion\u2010controlled docking step may be rate limiting. Our computation, based on the transient\u2010complex theory, identified the N\u2010terminal basic region of the <jats:styled-content style=\"fixed-case\">GBD<\/jats:styled-content> as the docking segment. However, several other changes in solvent conditions provided strong evidence that the coalescing step also contributed to determining the magnitude of <jats:italic>k<\/jats:italic><jats:sub>a<\/jats:sub>. Addition of glucose and trifluoroethanol and an increase in temperature all produced experimental <jats:italic>k<\/jats:italic><jats:sub>a<\/jats:sub> values much higher than expected from the effects on the docking rate alone. Conversely, addition of urea led to <jats:italic>k<\/jats:italic><jats:sub>a<\/jats:sub> values much lower than expected if only the docking rate was affected. These results all pointed to <jats:italic>k<\/jats:italic><jats:sub>a<\/jats:sub> being approximately two\u2010thirds of the docking rate constant under physiological solvent conditions.<\/jats:p>","DOI":"10.1111\/febs.14197","type":"journal-article","created":{"date-parts":[[2017,8,14]],"date-time":"2017-08-14T12:22:36Z","timestamp":1502713356000},"page":"3381-3391","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["The dock\u2010and\u2010coalesce mechanism for the association of a <scp>WASP<\/scp> disordered region with the Cdc42 <scp>GTP<\/scp>ase"],"prefix":"10.1111","volume":"284","author":[{"given":"Li","family":"Ou","sequence":"first","affiliation":[{"name":"Department of Physics and Institute of Molecular Biophysics Florida State University Tallahassee FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Megan","family":"Matthews","sequence":"additional","affiliation":[{"name":"Department 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