title: A structure-based mechanism for vesicle capture by the multisubunit tethering complex Dsl1.
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.
authors.affiliation: Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Ren
authors.forename: Calvin K
authors.initials: CK
authors.lastname: Yip
authors.forename: Arati
authors.initials: A
authors.lastname: Tripathi
authors.forename: David
authors.initials: D
authors.lastname: Huie
authors.forename: Philip D
authors.initials: PD
authors.lastname: Jeffrey
authors.forename: Thomas
authors.initials: T
authors.lastname: Walz
authors.forename: Frederick M
authors.initials: FM
authors.lastname: Hughson
mesh_terms: D018360:Crystallography, X-Ray; D004721:Endoplasmic Reticulum / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D050600:SNARE Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000737:chemistry*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism; D022161:Transport Vesicles / Q000378:metabolism*
chemical_list: C428365:DSL1 protein, S cerevisiae; D008565:Membrane Proteins; C506557:SEC39 protein, S cerevisiae; D050600:SNARE Proteins; D029701:Saccharomyces cerevisiae Proteins