2EQB: Crystal Structure Of The Rab Gtpase Sec4p, The Sec2p Gef Domain, And Phosphate Complex

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.
PDB ID: 2EQBDownload
MMDB ID: 46126
PDB Deposition Date: 2007/3/30
Updated in MMDB: 2012/11
Experimental Method:
x-ray diffraction
Resolution: 2.7  Å
Source Organism:
Similar Structures:
Biological Unit for 2EQB: trimeric; determined by author and by software (PISA)
Molecular Components in 2EQB
Label Count Molecule
Proteins (3 molecules)
Ras-related Protein Sec4(Gene symbol: SEC4)
Molecule annotation
RAB Guanine Nucleotide Exchange Factor Sec2(Gene symbol: SEC2)
Molecule annotation
Chemicals (2 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB