Molecular Basis for Recognition of Dilysine Trafficking Motifs by COPI

Citations Over TimeTop 10% of 2012 papers

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.

Related Papers

• → The endoplasmic reticulum—Golgi intermediate compartment(1992)230 cited
• → Evolution of the Endoplasmic Reticulum and the Golgi Complex(2007)14 cited
• → Ultrastructural analysis of transitional endoplasmic reticulum and pre-Golgi intermediates: a highway for cars and trucks(2003)31 cited
• → Pre-Golgi Intermediates(2010)
• → Endoplasmic Reticulum-Golgi Intermediate Compartment Protein 3(2020)