PDBsum entry 4j77

Protein transport

PDB id: 4j77

Contents

Protein chains

300 a.a.

Ligands

LYS-GLU-LYS-SER-ASP

ALA-LYS-GLU-LYS-SER-ASP

Waters ×599

References listed in PDB file

Key reference

• Title: Rules for the recognition of dilysine retrieval motifs by coatomer.
• Authors: W.Ma, J.Goldberg.
• Ref.: Embo J, 2013, 32, 926-937. [DOI no: 10.1038/emboj.2013.41]
• PubMed id: 23481256

Abstract

Cytoplasmic dilysine motifs on transmembrane proteins are captured by coatomer α-COP and β'-COP subunits and packaged into COPI-coated vesicles for Golgi-to-ER retrieval. Numerous ER/Golgi proteins contain K(x)Kxx motifs, but the rules for their recognition are unclear. We present crystal structures of α-COP and β'-COP bound to a series of naturally occurring retrieval motifs-encompassing KKxx, KxKxx and non-canonical RKxx and viral KxHxx sequences. Binding experiments show that α-COP and β'-COP have generally the same specificity for KKxx and KxKxx, but only β'-COP recognizes the RKxx signal. Dilysine motif recognition involves lysine side-chain interactions with two acidic patches. Surprisingly, however, KKxx and KxKxx motifs bind differently, with their lysine residues transposed at the binding patches. We derive rules for retrieval motif recognition from key structural features: the reversed binding modes, the recognition of the C-terminal carboxylate group which enforces lysine positional context, and the tolerance of the acidic patches for non-lysine residues.