The Structural Basis for Activation of the Rab Ypt1p by the TRAPP Membrane-Tethering Complexes

Yiying Cai, Harvey F. Chin, Darina Lazarova, Shekar Menon, Chunmei Fu, Huaqing Cai, Anthony Sclafani, David W. Rodgers, Enrique M. De La Cruz, Susan Ferro-Novick, Karin M. Reinisch

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1202-1213
Number of pages12
JournalCell
Volume133
Issue number7
DOIs
StatePublished - Jun 27 2008
Externally publishedYes

Keywords

  • CELLBIO
  • SIGNALING

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

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