A Structure-Based Mechanism for Vesicle Capture by the Multisubunit Tethering Complex Dsl1

Yi Ren, Calvin K. Yip, Arati Tripathi, David Huie, Philip D. Jeffrey, Thomas Walz, Frederick M. Hughson

Research output: Contribution to journalArticle

108 Scopus citations

Abstract

Vesicle trafficking requires membrane fusion, mediated by SNARE proteins, and upstream events that probably include "tethering," an initial long-range attachment between a vesicle and its target organelle. Among the factors proposed to mediate tethering are a set of multisubunit tethering complexes (MTCs). The Dsl1 complex, with only three subunits, is the simplest known MTC and is essential for the retrograde traffic of COPI-coated vesicles from the Golgi to the ER. To elucidate structural principles underlying MTC function, we have determined the structure of the Dsl1 complex, revealing a tower containing at its base the binding sites for two ER SNAREs and at its tip a flexible lasso for capturing vesicles. The Dsl1 complex binds to individual SNAREs via their N-terminal regulatory domains and also to assembled SNARE complexes; moreover, it is capable of accelerating SNARE complex assembly. Our results suggest that even the simplest MTC may be capable of orchestrating vesicle capture, uncoating, and fusion.

Original languageEnglish (US)
Pages (from-to)1119-1129
Number of pages11
JournalCell
Volume139
Issue number6
DOIs
StatePublished - Dec 11 2009

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Keywords

  • CELLBIO

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