RT Journal Article
SR Electronic
T1 A baton-relay and proofreading mechanism for selective ER retrieval signal capture by the KDEL receptor
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.03.21.436307
DO 10.1101/2021.03.21.436307
A1 Andreas Gerondopoulos
A1 Philipp Bräuer
A1 Tomoaki Sobajima
A1 Zhiyi Wu
A1 Joanne L. Parker
A1 Philip C. Biggin
A1 Francis A. Barr
A1 Simon Newstead
YR 2021
UL http://biorxiv.org/content/early/2021/03/23/2021.03.21.436307.abstract
AB The KDEL-retrieval pathway captures escaped ER proteins with a KDEL or variant C-terminal signal at acidic pH in the Golgi and releases them at neutral pH in the ER. To address the mechanism of signal binding and the molecular basis for differences in signal affinity, we determined the HDEL and RDEL bound structures of the KDEL-receptor. Affinity differences are explained by interactions between the variable −4 position of the signal and W120, whereas initial capture of retrieval signals by their carboxyl-terminus is mediated by a baton-relay mechanism involving a series of conserved arginine residues in the receptor. This explains how the signal is first captured and then pulled into the binding cavity. During capture, retrieval signals undergo a selective proofreading step involving two gatekeeper residues D50 and E117 in the receptor. These mechanisms operate upstream of the pH-dependent closure of the receptor and explain the selectivity of the KDEL-retrieval pathway.Competing Interest StatementThe authors have declared no competing interest.