Structural highlights
Function
[COPD_YEAST] The coatomer is a cytosolic protein complex that binds to dilysine motifs and reversibly associates with Golgi non-clathrin-coated vesicles, which further mediate biosynthetic protein transport from the ER, via the Golgi up to the trans Golgi network. Coatomer complex is required for budding from Golgi membranes, and is essential for the retrograde Golgi-to-ER transport of dilysine-tagged proteins (By similarity). [DSL1_YEAST] Required for protein transport between the Golgi and the endoplasmic reticulum. May tether coatomer-coated retrograde transport vesicles to the ER membrane through interaction with coatomer as well as the SNARE complex. May contribute to the stabilization of the SNARE complex.[1] [2] [3]
Publication Abstract from PubMed
Coatomer consists of two subcomplexes: the membrane-targeting, ADP ribosylation factor 1 (Arf1):GTP-binding betagammadeltazeta-COP F-subcomplex, which is related to the adaptor protein (AP) clathrin adaptors, and the cargo-binding alphabeta'epsilon-COP B-subcomplex. We present the structure of the C-terminal mu-homology domain of the yeast delta-COP subunit in complex with the WxW motif from its binding partner, the endoplasmic reticulum-localized Dsl1 tether. The motif binds at a site distinct from that used by the homologous AP mu subunits to bind YxxPhi cargo motifs with its two tryptophan residues sitting in compatible pockets. We also show that the Saccharomyces cerevisiae Arf GTPase-activating protein (GAP) homolog Gcs1p uses a related WxxF motif at its extreme C terminus to bind to delta-COP at the same site in the same way. Mutations designed on the basis of the structure in conjunction with isothermal titration calorimetry confirm the mode of binding and show that mammalian delta-COP binds related tryptophan-based motifs such as that from ArfGAP1 in a similar manner. We conclude that delta-COP subunits bind Wxn(1-6)[WF] motifs within unstructured regions of proteins that influence the lifecycle of COPI-coated vesicles; this conclusion is supported by the observation that, in the context of a sensitizing domain deletion in Dsl1p, mutating the tryptophan-based motif-binding site in yeast causes defects in both growth and carboxypeptidase Y trafficking/processing.
Structural basis for the binding of tryptophan-based motifs by delta-COP.,Suckling RJ, Poon PP, Travis SM, Majoul IV, Hughson FM, Evans PR, Duden R, Owen DJ Proc Natl Acad Sci U S A. 2015 Nov 17;112(46):14242-7. doi:, 10.1073/pnas.1506186112. Epub 2015 Nov 2. PMID:26578768[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Vanrheenen SM, Reilly BA, Chamberlain SJ, Waters MG. Dsl1p, an essential protein required for membrane traffic at the endoplasmic reticulum/Golgi interface in yeast. Traffic. 2001 Mar;2(3):212-31. PMID:11260526
- ↑ Andag U, Neumann T, Schmitt HD. The coatomer-interacting protein Dsl1p is required for Golgi-to-endoplasmic reticulum retrieval in yeast. J Biol Chem. 2001 Oct 19;276(42):39150-60. Epub 2001 Aug 7. PMID:11493604 doi:http://dx.doi.org/10.1074/jbc.M105833200
- ↑ Reilly BA, Kraynack BA, VanRheenen SM, Waters MG. Golgi-to-endoplasmic reticulum (ER) retrograde traffic in yeast requires Dsl1p, a component of the ER target site that interacts with a COPI coat subunit. Mol Biol Cell. 2001 Dec;12(12):3783-96. PMID:11739780
- ↑ Suckling RJ, Poon PP, Travis SM, Majoul IV, Hughson FM, Evans PR, Duden R, Owen DJ. Structural basis for the binding of tryptophan-based motifs by delta-COP. Proc Natl Acad Sci U S A. 2015 Nov 17;112(46):14242-7. doi:, 10.1073/pnas.1506186112. Epub 2015 Nov 2. PMID:26578768 doi:http://dx.doi.org/10.1073/pnas.1506186112
