Structural highlights
4zdw is a 3 chain structure with sequence from Baker's yeast. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Ligands: | |
| Gene: | SEC4, SRO6, YFL005W (Baker's yeast), SEC2, YNL272C, N0641 (Baker's yeast) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[SEC4_YEAST] Involved in exocytosis. Maybe by regulating the binding and fusion of secretory vesicles with the cell surface. The GTP-bound form of SEC4 may interact with an effector, thereby stimulating its activity and leading to exocytotic fusion. SEC4 may be an upstream activator of the 19.5S SEC8/SEC15 particle. SEC4 probably interacts directly with SEC8; it could serve as the attachment site for the SEC8/SEC15 particle.[1] [SEC2_YEAST] Guanine nucleotide exchange factor for SEC4, catalyzing the dissociation of GDP from SEC4 and also potently promoting binding of GTP. Activation of SEC4 by SEC2 is needed for the directed transport of vesicles to sites of exocytosis. Binds the Rab GTPase YPT32, but does not have exhange activity on YPT32.[2] [3] [4]
Publication Abstract from PubMed
BACKGROUND: Sec4p is a small monomeric Ras-related GTP-binding protein (23 kDa) that regulates polarized exocytosis in S. cerevisiae. In this study we examine the structural effects of a conserved serine residue in the P-loop corresponding to G12 in Ras. RESULTS: We show that the Sec4p residue serine 29 forms a hydrogen bond with the nucleotide. Mutations of this residue have a different impact than equivalent mutations in Ras and can form stable associations with the exchange factor allowing us to elucidate the structure of a complex of Sec4p bound to the exchange factor Sec2p representing an early stage of the exchange reaction. CONCLUSIONS: Our structural investigation of the Sec4p-Sec2p complex reveals the role of the Sec2p coiled-coil domain in facilitating the fast kinetics of the exchange reaction. For Ras-family GTPases, single point mutations that impact the signaling state of the molecule have been well described however less structural information is available for equivalent mutations in the case of Rab proteins. Understanding the structural properties of mutants such as the one described here, provides useful insights into unique aspects of Rab GTPase function.
New insights into the molecular mechanism of the Rab GTPase Sec4p activation.,Rinaldi FC, Packer M, Collins R BMC Struct Biol. 2015 Aug 12;15:14. doi: 10.1186/s12900-015-0041-5. PMID:26263895[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Grosshans BL, Andreeva A, Gangar A, Niessen S, Yates JR 3rd, Brennwald P, Novick P. The yeast lgl family member Sro7p is an effector of the secretory Rab GTPase Sec4p. J Cell Biol. 2006 Jan 2;172(1):55-66. PMID:16390997 doi:http://dx.doi.org/10.1083/jcb.200510016
- ↑ Walch-Solimena C, Collins RN, Novick PJ. Sec2p mediates nucleotide exchange on Sec4p and is involved in polarized delivery of post-Golgi vesicles. J Cell Biol. 1997 Jun 30;137(7):1495-509. PMID:9199166
- ↑ Elkind NB, Walch-Solimena C, Novick PJ. The role of the COOH terminus of Sec2p in the transport of post-Golgi vesicles. J Cell Biol. 2000 Apr 3;149(1):95-110. PMID:10747090
- ↑ Ortiz D, Medkova M, Walch-Solimena C, Novick P. Ypt32 recruits the Sec4p guanine nucleotide exchange factor, Sec2p, to secretory vesicles; evidence for a Rab cascade in yeast. J Cell Biol. 2002 Jun 10;157(6):1005-15. Epub 2002 Jun 3. PMID:12045183 doi:http://dx.doi.org/10.1083/jcb.200201003
- ↑ Rinaldi FC, Packer M, Collins R. New insights into the molecular mechanism of the Rab GTPase Sec4p activation. BMC Struct Biol. 2015 Aug 12;15:14. doi: 10.1186/s12900-015-0041-5. PMID:26263895 doi:http://dx.doi.org/10.1186/s12900-015-0041-5
