The exocyst complex is a hetero-octameric protein complex that functions during cell polarization by tethering the secretory vesicle to the target membrane. The yeast exocyst subunit Sec3 binds to phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P(2)) and the small GTPases Rho1 and Cdc42 via its N-terminal domain (Sec3-N), and these interactions target Sec3 to the plasma membrane. Here we report the crystal structure of the Sec3-N in complex with Rho1 at 2.6-A resolution. Sec3-N adopts a pleckstrin homology (PH) fold, despite having no detectable sequence homology with other PH domains of known structure. Clusters of conserved basic residues constitute a positively charged cleft, which was identified as a binding site for PtdIns(4,5)P(2). Residues Phe77, Ile115 and Leu131 of Sec3 bind to an extended hydrophobic surface formed around switch regions I and II of Rho1. To our knowledge, these are the first structural insights into how an exocyst subunit might interact with both protein and phospholipid factors on the target membrane.

• PMID: 20062059
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Journal Article | Research Support, Non-U.S. Gov't

Authors

Yamashita M, Kurokawa K, Sato Y, Yamagata A, Mimura H, Yoshikawa A, Sato K, Nakano A, Fukai S

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