5FJX

Yeast delta-COP-I mu-homology domain complexed with Gcs1 WxxF peptide

Summary for 5FJX

• Entry DOI: 10.2210/pdb5fjx/pdb
• Related: 5FJW 5FJZ 5FK0
• Descriptor: COATOMER SUBUNIT DELTA, ADP-RIBOSYLATION FACTOR GTPASE-ACTIVATING PROTEIN GCS1 (3 entities in total)
• Functional Keywords: protein transport, cop-i, vesicle coat protein
• Biological source: SACCHAROMYCES CEREVISIAE (BAKER'S YEAST); More
• Cellular location: Cytoplasm : P43621 P35197
• Total number of polymer chains: 5
• Total formula weight: 92193.04

Authors

Suckling, R.J.,Evans, P.R.,Owen, D.J. (deposition date: 2015-10-13, release date: 2015-11-11, Last modification date: 2024-10-16)

Primary citation

Suckling, R.J.,Poon, P.P.,Travis, S.M.,Majoul, I.V.,Hughson, F.M.,Evans, P.R.,Duden, R.,Owen, D.J.
Structural Basis for the Binding of Tryptophan-Based Motifs by Delta-Cop.
Proc.Natl.Acad.Sci.USA, 112:14242-, 2015

PubMed Abstract: Coatomer consists of two subcomplexes: the membrane-targeting, ADP ribosylation factor 1 (Arf1):GTP-binding βγδζ-COP F-subcomplex, which is related to the adaptor protein (AP) clathrin adaptors, and the cargo-binding αβ'ε-COP B-subcomplex. We present the structure of the C-terminal μ-homology domain of the yeast δ-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 μ subunits to bind YxxΦ 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 δ-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 δ-COP binds related tryptophan-based motifs such as that from ArfGAP1 in a similar manner. We conclude that δ-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.

PubMed: 26578768
DOI: 10.1073/PNAS.1506186112

Experimental method

X-RAY DIFFRACTION (2.45 Å)