Identification of amino acids in the binding pocket of the human KDEL receptor.

The Journal of Biological Chemistry
A A Scheel, H R Pelham

Abstract

Retention of soluble proteins in the endoplasmic reticulum is dependent on their interaction with the KDEL (Lys-Asp-Glu-Leu) receptor in the Golgi apparatus and their subsequent retrieval back to the endoplasmic reticulum. We have studied the three-dimensional organization of the human KDEL receptor using site-directed mutagenesis and sulfhydryl-specific labeling. We have identified four amino acid residues, Arg-5, Asp-50, Tyr-162, and Asn-165, which we suggest participate in the formation of the ligand binding pocket. Arg-5 and Asp-50 are shown to be located on the lumenal side of the membrane and are inaccessible from the cytoplasm. In addition, our results strongly support a topology of the KDEL receptor similar to the family of G-protein-coupled receptors with seven transmembrane domains. Furthermore, Asp-50 plays a crucial role in the binding of His/Lys-Asp-Glu-Leu ligands, but is not required for Asp-Asp-Glu-Leu binding, suggesting that this residue forms an ion pair with the positively charged amino acid residue positioned 4 residues from the carboxyl terminus of the ligand.

References

Mar 5, 1992·Journal of Molecular Biology·J C Semenza, H R Pelham
Aug 20, 1992·Journal of Molecular Biology·M J Lewis, H R Pelham
Dec 1, 1990·Trends in Biochemical Sciences·H R Pelham
Nov 8, 1990·Nature·M J Lewis, H R Pelham
Jan 1, 1987·Methods in Enzymology·T A KunkelR A Zakour
Jan 13, 1995·The Journal of Biological Chemistry·T W Loo, D M Clarke
May 1, 1993·European Journal of Biochemistry·L Sipos, G von Heijne
Dec 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·H I LeeN V Raikhel
Oct 1, 1993·Molecular and Cellular Biology·P SinghW Hong
Aug 6, 1996·Biochemistry·A A Scheel, H R Pelham
Sep 1, 1996·The Journal of Cell Biology·B SönnichsenG Warren

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Citations

Oct 17, 2006·The Journal of Membrane Biology·J BéthuneJ Moelleken
Dec 5, 1998·Biochimica Et Biophysica Acta·S B Shears
Jul 22, 2008·Nature Cell Biology·Teodoro PulvirentiAlberto Luini
Oct 1, 2003·Molecular Biology of the Cell·Margarita CabreraAngel Velasco
Nov 18, 2003·Molecular Biology of the Cell·Sylvie Le GallTom Rapoport
Sep 11, 2001·The Plant Cell·B A PhillipsonJ Denecke
Feb 11, 2005·Eukaryotic Cell·Stacy L PflugerKristin M Hager
Oct 12, 2004·Annual Review of Cell and Developmental Biology·Marcus C S LeeRandy Schekman
Nov 10, 2013·PloS One·Elliott W AbramsDeborah J Andrew
Feb 12, 2013·Genetics·Charles K Barlowe, Elizabeth A Miller
Mar 24, 1999·Molecular Membrane Biology·R T Cowling, H C Birnboim
Oct 27, 2009·FEBS Letters·Mirco Capitani, Michele Sallese
Jan 7, 2016·Frontiers in Immunology·Daisuke KamimuraMasaaki Murakami
Jul 17, 2004·The Plant Journal : for Cell and Molecular Biology·Kentaro TamuraIkuko Hara-Nishimura
Oct 23, 2008·The Plant Journal : for Cell and Molecular Biology·Thorsten BrachAndreas J Meyer
Jun 18, 2015·Nature Communications·Daisuke KamimuraMasaaki Murakami
Jun 13, 2015·BioMed Research International·Monica GiannottaMichele Sallese
Aug 24, 2006·The Journal of Biological Chemistry·Irene BrunkGudrun Ahnert-Hilger
Jul 26, 2019·Cellular and Molecular Neurobiology·Zhangyuan LiaoWenliang Li
Feb 15, 2017·Proceedings of the National Academy of Sciences of the United States of America·Alexander R FrenchRonald S Rock
Jun 27, 1998·Biochemical and Biophysical Research Communications·I M JansonP Ek

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