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PMID: 18585354 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

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

Cell ·Vol. 133 ·No. 7 ·2008-06-27 ·Pages 1202-13

Cai Y, Chin HF, Lazarova D, Menon S, Fu C, Cai H, Sclafani A, Rodgers DW, De La Cruz EM, Ferro-Novick S, Reinisch KM

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.

MeSH Terms
Endoplasmic Reticulum/metabolism Enzyme Activation Golgi Apparatus/metabolism Guanine Nucleotide Exchange Factors/chemistry,metabolism Models, Molecular Protein Interaction Mapping Saccharomyces cerevisiae/cytology,enzymology,metabolism Saccharomyces cerevisiae Proteins/chemistry,genetics,metabolism Vesicular Transport Proteins/chemistry,genetics,metabolism rab GTP-Binding Proteins/chemistry,metabolism
Chemicals
Guanine Nucleotide Exchange Factors Saccharomyces cerevisiae Proteins Vesicular Transport Proteins transport protein particle, TRAPP YPT1 protein, S cerevisiae rab GTP-Binding Proteins
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Cai Yiying
Department of Cell Biology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA.
Chin Harvey F
Lazarova Darina
Menon Shekar
Fu Chunmei
Cai Huaqing
Sclafani Anthony
Rodgers David W
De La Cruz Enrique M
Ferro-Novick Susan
Reinisch Karin M
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Article Info
Journal
Cell
Abbr.
Cell
ISSN
1097-4172
DOI
10.1016/j.cell.2008.04.049
Published
2008-06-27
Pages
1202-13
Language
English
Region
United States
NLM ID
0413066
PMCID
PMC2465810
Subset
IM
Grants
NINDS NIH HHS · R01 NS038041 · United States
NIGMS NIH HHS · GM071688 · United States
NIDA NIH HHS · R01 DA002243 · United States
NIGMS NIH HHS · T32-GM07223 · United States
Howard Hughes Medical Institute · United States
NINDS NIH HHS · R56 NS038041 · United States
NCRR NIH HHS · RR020171 · United States
NIDCD NIH HHS · F31 DC009143-01 · United States
NIGMS NIH HHS · R01 GM071688 · United States
NIDCD NIH HHS · F31 DC009143 · United States
NCRR NIH HHS · P20 RR020171 · United States
NIDCD NIH HHS · 1F31DC009143-01 · United States
NINDS NIH HHS · R01 NS038041-04 · United States
NIGMS NIH HHS · R01 GM071688-02 · United States
NIDA NIH HHS · DA02243 · United States
NIGMS NIH HHS · R01 GM080616 · United States
NIGMS NIH HHS · GM080616 · United States
NIGMS NIH HHS · R01 GM080616-01 · United States
NINDS NIH HHS · NS38041 · United States
Databases
PDB
3CUE
Corrections
CommentIn
PMID: 18585348
External Links
PubMed source DOI: 10.1016/j.cell.2008.04.049 PMC Full Text View journal details
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