Molecular basis for recognition of dilysine trafficking motifs by COPI

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

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.

MeSH terms

  • Amino Acid Motifs
  • Binding Sites
  • Coat Protein Complex I / chemistry
  • Coat Protein Complex I / genetics
  • Coat Protein Complex I / metabolism*
  • Coatomer Protein / chemistry
  • Coatomer Protein / genetics
  • Coatomer Protein / metabolism*
  • Dipeptides / metabolism*
  • Endoplasmic Reticulum / metabolism
  • Golgi Apparatus / metabolism
  • Models, Molecular
  • Protein Binding
  • Protein Transport
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / chemical synthesis
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism

Substances

  • Coat Protein Complex I
  • Coatomer Protein
  • Dipeptides
  • Saccharomyces cerevisiae Proteins
  • lysyllysine

Associated data

  • PDB/2YNN
  • PDB/2YNO
  • PDB/2YNP