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Dev Cell. 2012 Dec 11;23(6):1255-62. doi: 10.1016/j.devcel.2012.10.017. Epub 2012 Nov 21.

Molecular basis for recognition of dilysine trafficking motifs by COPI.

Author information

1
Cambridge Institute for Medical Research, Department of Clinical Biochemistry, University of Cambridge, Hills Road, Cambridge CB2 0XY, UK. lpj21@cam.ac.uk

Abstract

COPI mediates retrograde trafficking from the Golgi to the endoplasmic reticulum (ER) and within the Golgi stack, sorting transmembrane proteins bearing C-terminal KKxx or KxKxx motifs. The structure of KxKxx motifs bound to the N-terminal WD-repeat domain of β'-COP identifies electrostatic contacts between the motif and complementary patches at the center of the β'-COP propeller. An absolute requirement of a two-residue spacing between the terminal carboxylate group and first lysine residue results from interactions of carbonyl groups in the motif backbone with basic side chains of β'-COP. Similar interactions are proposed to mediate binding of KKxx motifs by the homologous α-COP domain. Mutation of key interacting residues in either domain or in their cognate motifs abolishes in vitro binding and results in mistrafficking of dilysine-containing cargo in yeast without compromising cell viability. Flexibility between β'-COP WD-repeat domains and the location of cargo binding have implications for COPI coat assembly.

PMID:
23177648
PMCID:
PMC3521961
DOI:
10.1016/j.devcel.2012.10.017
[Indexed for MEDLINE]
Free PMC Article

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