2EQB

Crystal structure of the Rab GTPase Sec4p, the Sec2p GEF domain, and phosphate complex

Summary for 2EQB

• Entry DOI: 10.2210/pdb2eqb/pdb
• Related: 2E7S 2OCY
• Descriptor: Ras-related protein SEC4, Rab guanine nucleotide exchange factor SEC2, PHOSPHATE ION, ... (4 entities in total)
• Functional Keywords: coiled coil, endocytosis-exocytosis complex, endocytosis/exocytosis
• Biological source: Saccharomyces cerevisiae (baker's yeast); More
• Cellular location: Cytoplasmic vesicle, secretory vesicle membrane; Lipid-anchor; Cytoplasmic side: P07560; Bud neck: P17065
• Total number of polymer chains: 3
• Total formula weight: 42420.28

Authors

Sato, Y.,Fukai, S.,Ishitani, R.,Nureki, O. (deposition date: 2007-03-30, release date: 2007-05-22, Last modification date: 2024-03-13)

Primary citation

Sato, Y.,Fukai, S.,Ishitani, R.,Nureki, O.
Crystal structure of the Sec4p{middle dot}Sec2p complex in the nucleotide exchanging intermediate state
Proc.Natl.Acad.Sci.Usa, 104:8305-8310, 2007

PubMed Abstract: 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 A 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 A structure of the Sec4p.Sec2p complex, our structure contains a phosphate ion bound to the P-loop, which may represent an intermediate state of the nucleotide exchange reaction.

PubMed: 17488829
DOI: 10.1073/pnas.0701550104

Experimental method

X-RAY DIFFRACTION (2.7 Å)