{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T07:08:48Z","timestamp":1761894528273},"reference-count":43,"publisher":"Proceedings of the National Academy of Sciences","issue":"20","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2007,5,15]]},"abstract":"<jats:p>Vesicular transport during exocytosis is regulated by Rab GTPase (Sec4p in yeast), which is activated by a guanine nucleotide exchange factor (GEF) called Sec2p. Here, we report the crystal structure of the Sec2p GEF domain in a complex with the nucleotide-free Sec4p at 2.7 \u212b resolution. Upon complex formation, the Sec2p helices approach each other, flipping the side chain of Phe-109 toward Leu-104 and Leu-108 of Sec2p. These three residues provide a hydrophobic platform to attract the side chains of Phe-49, Ile-53, and Ile-55 in the switch I region as well as Phe-57 and Trp-74 in the interswitch region of Sec4p. Consequently, the switch I and II regions are largely deformed, to create a flat hydrophobic interface that snugly fits the surface of the Sec2p coiled coil. These drastic conformational changes disrupt the interactions between switch I and the bound guanine nucleotide, which facilitates the GDP release. Unlike the recently reported 3.3 \u212b structure of the Sec4p\u00b7Sec2p complex, our structure contains a phosphate ion bound to the P-loop, which may represent an intermediate state of the nucleotide exchange reaction.<\/jats:p>","DOI":"10.1073\/pnas.0701550104","type":"journal-article","created":{"date-parts":[[2007,5,9]],"date-time":"2007-05-09T02:38:41Z","timestamp":1178678321000},"page":"8305-8310","update-policy":"http:\/\/dx.doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":48,"title":["Crystal structure of the Sec4p\u00b7Sec2p complex in the nucleotide exchanging intermediate state"],"prefix":"10.1073","volume":"104","author":[{"given":"Yusuke","family":"Sato","sequence":"first","affiliation":[{"name":"*Department of Biological Information, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama-shi, Kanagawa 226-8501, Japan; and"}]},{"given":"Shuya","family":"Fukai","sequence":"additional","affiliation":[{"name":"*Department of Biological Information, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama-shi, Kanagawa 226-8501, Japan; and"},{"name":"Center for Biological Resources and Informatics, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama-shi, Kanagawa 226-8501, Japan"}]},{"given":"Ryuichiro","family":"Ishitani","sequence":"additional","affiliation":[{"name":"*Department of Biological Information, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama-shi, Kanagawa 226-8501, Japan; and"}]},{"given":"Osamu","family":"Nureki","sequence":"additional","affiliation":[{"name":"*Department of Biological Information, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama-shi, Kanagawa 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