Contribution of the second transmembrane helix of the secretin receptor to the positioning of secretin

FEBS Letters
E Di PaoloP Robberecht

Abstract

The secretin amino-terminal residues are essential for high affinity binding to its cognate receptor and for its biological activity. Mutation of the [Asp3] residue of secretin to [Asn3] decreased the ligand's affinity for the rat wild-type receptor 100-300-fold. Receptor mutations in the transmembrane 2 domain and the beginning of the first extracellular loop allowed the identification of three residues involved in recognition of the [Asp3] residue: D174, K173 and R166. Mutation of K173 and D174 not only reduced the secretin and [Asn3]secretin affinities, but also changed the receptor's selectivity as judged by a decreased secretin and [Asn3]secretin potency ratio. The most striking effect was observed when R166 was mutated to Q, D or L. This led to receptors with a very low affinity for secretin but an up to 10-fold higher affinity than the wild-type receptor for [Asn3]secretin. This suggested that R166, highly conserved in that subgroup of receptor, is a major determinant for the recognition of the [Asp3] of the ligand.

References

Sep 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·B Thorens
Jun 26, 1995·Biochemical and Biophysical Research Communications·J P VilardagaP Robberecht
Oct 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·R ChenW W Vale
Dec 15, 1994·Regulatory Peptides·E CiccarelliP Robberecht
Jul 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·J R Pisegna, S A Wank
Jan 26, 1996·Biochemical and Biophysical Research Communications·J P VilardagaP Robberecht

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Citations

Jun 25, 2003·Computational Biology and Chemistry·William R TaylorRobert P Bywater
Jul 19, 2013·Nature·Fai Yiu SiuRaymond C Stevens
Mar 13, 2013·Proceedings of the National Academy of Sciences of the United States of America·Denise WoottenPatrick M Sexton
Sep 12, 2012·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Maoqing DongLaurence J Miller
May 27, 2010·Journal of Endocrinological Investigation·D H St-Pierre, F Broglio
Dec 24, 2013·Trends in Pharmacological Sciences·Kaspar HollensteinRaymond C Stevens
Nov 26, 2015·Frontiers in Pharmacology·Kelly J CulhaneElsa C Y Yan
May 6, 2011·British Journal of Pharmacology·Laurence J MillerKaleeckal G Harikumar
Jun 9, 2011·British Journal of Pharmacology·James BarwellDebbie L Hay
Mar 23, 2012·Biochemical Society Transactions·James BarwellDavid R Poyner
Sep 20, 2016·Current Opinion in Pharmacology·Arnau CordomíIrina G Tikhonova
Dec 3, 2011·Pharmacology·Christina Rye UnderwoodSteffen Reedtz-Runge
Aug 20, 2020·Nature Communications·Maoqing DongLaurence J Miller
Feb 24, 2001·Annals of the New York Academy of Sciences·P RobberechtM Waelbroeck
Jun 3, 2018·Hormones : International Journal of Endocrinology and Metabolism·Vlasios KarageorgosGeorge Liapakis
Aug 26, 2006·Regulatory Peptides·Francis K Y SiuBilly K C Chow

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