1. Structure-Function Study of the N-terminal Domain of Exocyst Subunit Sec3*
- Author
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Trevor J. Foskett, Andreas Knödler, Jian Zhang, Sung Haeng Lee, Wei Guo, Kyuwon Baek, Xiaoyu Zhang, Kelly Orlando, and Roberto Dominguez
- Subjects
Protein Folding ,Saccharomyces cerevisiae Proteins ,Molecular Sequence Data ,Exocyst ,GTPase ,Saccharomyces cerevisiae ,Biology ,Crystallography, X-Ray ,Biochemistry ,Exocytosis ,Cell membrane ,Structure-Activity Relationship ,medicine ,Small GTPase ,Amino Acid Sequence ,Molecular Biology ,Phospholipids ,Binding Sites ,Sequence Homology, Amino Acid ,Glucan Endo-1,3-beta-D-Glucosidase ,Cell Membrane ,Cell Biology ,Cell biology ,Pleckstrin homology domain ,medicine.anatomical_structure ,Mutation ,Phospholipid Binding ,Protein folding ,Crystallization ,Dimerization - Abstract
The exocyst is an evolutionarily conserved octameric complex involved in polarized exocytosis from yeast to humans. The Sec3 subunit of the exocyst acts as a spatial landmark for exocytosis through its ability to bind phospholipids and small GTPases. The structure of the N-terminal domain of Sec3 (Sec3N) was determined ab initio and defines a new subclass of pleckstrin homology (PH) domains along with a new family of proteins carrying this domain. Respectively, N- and C-terminal to the PH domain Sec3N presents an additional alpha-helix and two beta-strands that mediate dimerization through domain swapping. The structure identifies residues responsible for phospholipid binding, which when mutated in cells impair the localization of exocyst components at the plasma membrane and lead to defects in exocytosis. Through its ability to bind the small GTPase Cdc42 and phospholipids, the PH domain of Sec3 functions as a coincidence detector at the plasma membrane.
- Published
- 2010