W.Ma
and
J.Goldberg
(2013).
Rules for the recognition of dilysine retrieval motifs by coatomer.
Embo J,
32,
926-937.
PubMed id: 23481256
DOI: 10.1038/emboj.2013.41
Rules for the recognition of dilysine retrieval motifs by coatomer.
W.Ma,
J.Goldberg.
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.
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