The structural basis for activation of the Rab Ypt1p by the TRAPP membrane-tethering complexes

被引：146

作者：

Cai, Yiying ^{[1
,4
]}

Chin, Harvey F. ^{[2
]}

Lazarova, Darina ^{[1
,4
]}

Menon, Shekar ^{[1
,4
]}

Fu, Chunmei ^{[1
]}

Cai, Huaqing ^{[1
,4
]}

Sclafani, Anthony ^{[1
,4
]}

Rodgers, David W. ^{[3
]}

De La Cruz, Enrique M. ^{[2
]}

Ferro-Novick, Susan ^{[1
,4
]}

Reinisch, Karin M. ^{[1
]}

机构：

[1] Yale Univ, Sch Med, Dept Cell Biol, New Haven, CT 06520 USA

[2] Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA

[3] Univ Kentucky, Dept Mol & Cellular Biochem, Coll Med, Lexington, KY 40536 USA

[4] Yale Univ, Howard Hughes Med Inst, Dept Cell Biol, Sch Med, New Haven, CT 06519 USA

来源：

CELL | 2008年 / 133卷 / 07期

关键词：

D O I：

10.1016/j.cell.2008.04.049

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The multimeric membrane-tethering complexes TRAPPI and TRAPPII share seven subunits, of which four (Bet3p, Bet5p, Trs23p, and Trs31p) are minimally needed to activate the Rab GTPase Ypt1p in an event preceding membrane fusion. Here, we present the structure of a heteropentameric TRAPPI assembly complexed with Ypt1p. We propose that TRAPPI facilitates nucleotide exchange primarily by stabilizing the nucleotide-binding pocket of Ypt1p in an open, solvent-accessible form. Bet3p, Bet5p, and Trs23p interact directly with Ypt1p to stabilize this form, while the C terminus of Bet3p invades the pocket to participate in its remodeling. The Trs31p subunit does not interact directly with the GTPase but allosterically regulates the TRAPPI interface with Ypt1p. Our findings imply that TRAPPII activates Ypt1p by an identical mechanism. This view of a multimeric membrane-tethering assembly complexed with a Rab provides a framework for understanding events preceding membrane fusion at the molecular level.

引用

页码：1202 / 1213

页数：12