A SNARE-adaptor interaction is a new mode of cargo recognition in clathrin-coated vesicles

Miller, Sharon E., Collins, Brett M., McCoy, Airlie J., Robinson, Margaret S. and Owen, David J. (2007) A SNARE-adaptor interaction is a new mode of cargo recognition in clathrin-coated vesicles. Nature, 450 7169: 570-574. doi:10.1038/nature06353

Author Miller, Sharon E.
Collins, Brett M.
McCoy, Airlie J.
Robinson, Margaret S.
Owen, David J.
Title A SNARE-adaptor interaction is a new mode of cargo recognition in clathrin-coated vesicles
Journal name Nature   Check publisher's open access policy
ISSN 0028-0836
Publication date 2007-11-21
Sub-type Article (original research)
DOI 10.1038/nature06353
Volume 450
Issue 7169
Start page 570
End page 574
Total pages 5
Place of publication London, U.K.
Publisher Nature Publishing Group
Language eng
Subject 270000 Biological Sciences
0601 Biochemistry and Cell Biology
Abstract Soluble NSF attachment protein receptors (SNAREs) are type II transmembrane proteins that have critical roles in providing the specificity and energy for transport-vesicle fusion and must therefore be correctly partitioned between vesicle and organelle membranes(1-3). Like all other cargo, SNAREs need to be sorted into the forming vesicles by direct interaction with components of the vesicles' coats. Here we characterize the molecular details governing the sorting of a SNARE into clathrin-coated vesicles, namely the direct recognition of the three-helical bundle H-abc domain of the mouse SNARE Vti1b by the human clathrin adaptor epsinR (EPNR, also known as CLINT1). Structures of each domain and of their complex show that this interaction ( dissociation constant 22 mu M) is mediated by surface patches composed of approximately 15 residues each, the topographies of which are dependent on each domain's overall fold. Disruption of the interface with point mutations abolishes the interaction in vitro and causes Vti1b to become relocalized to late endosomes and lysosomes. This new class of highly specific, surface-surface interaction between the clathrin coat component and the cargo is distinct from the widely observed binding of short, linear cargo motifs by the assembly polypeptide (AP) complex and GGA adaptors(4) and is therefore not vulnerable to competition from standard motif-containing cargoes for incorporation into clathrin-coated vesicles. We propose that conceptually similar but mechanistically different interactions will direct the post-Golgi trafficking of many SNAREs.
Keyword Multidisciplinary Sciences
Homology enth domains
Trans-golgi network
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 71 times in Thomson Reuters Web of Science Article | Citations
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Created: Tue, 19 Feb 2008, 01:44:46 EST