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Structural basis for pH-dependent retrieval of ER proteins from the Golgi by the KDEL receptor

DOI: 10.1126/science.aaw2859 DOI Help

Authors: Philipp Braeuer (University of Oxford) , Joanne L. Parker (University of Oxford) , Andreas Gerondopoulos (University of Oxford) , Iwan Zimmermann (University of Zurich) , Markus A. Seeger (University of Zurich) , Francis A. Barr (University of Oxford) , Simon Newstead (University of Oxford)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Science , VOL 363 , PAGES 1103 - 1107

State: Published (Approved)
Published: March 2019
Diamond Proposal Number(s): 18069

Abstract: Selective export and retrieval of proteins between the endoplasmic reticulum (ER) and Golgi apparatus is indispensable for eukaryotic cell function. An essential step in the retrieval of ER luminal proteins from the Golgi is the pH-dependent recognition of a carboxyl-terminal Lys-Asp-Glu-Leu (KDEL) signal by the KDEL receptor. Here, we present crystal structures of the chicken KDEL receptor in the apo ER state, KDEL-bound Golgi state, and in complex with an antagonistic synthetic nanobody (sybody). These structures show a transporter-like architecture that undergoes conformational changes upon KDEL binding and reveal a pH-dependent interaction network crucial for recognition of the carboxyl terminus of the KDEL signal. Complementary in vitro binding and in vivo cell localization data explain how these features create a pH-dependent retrieval system in the secretory pathway.

Subject Areas: Medicine

Instruments: I24-Microfocus Macromolecular Crystallography