Prostanoid receptors belong to the class of heptahelical plasma membrane receptors. For the five prostanoids, eight receptor subtypes have been identified. They display an overall sequence similarity of roughly 30%. Based on sequence comparison, single amino acids in different subtypes of different species have previously been identified by site-directed mutagenesis or in hybrid receptors that appear to be essential for ligand binding or G-protein coupling. Based on this information, a series of mutants of the human FP receptor was generated and characterized in ligand-binding and second-messenger-formation studies. It was found that mutation of His-81 to Ala in transmembrane domain 2 and of Arg-291 to Leu in transmembrane domain 7, which are putative interaction partners for the prostanoid's carboxyl group, abolished ligand binding. Mutants in which Ser-263 in transmembrane domain 6 or Asp-300 in transmembrane domain 7 had been replaced by Ala or Gln, respectively, no longer discriminated between prostaglandins PGF2α and PGD2. Thus distortion of the topology of transmembrane domains 6 and 7 appears to interfere with the cyclopentane ring selectivity of the receptor. PGF2α-induced inositol formation was strongly reduced in the mutant Asp-300Gln, inferring a role for this residue in agonist-induced G-protein activation.
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April 2003
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Research Article|
April 15 2003
Identification by site-directed mutagenesis of amino acids contributing to ligand-binding specificity or signal transduction properties of the human FP prostanoid receptor
Frank NEUSCHÄFER-RUBE;
Frank NEUSCHÄFER-RUBE
Universität Potsdam, Institut für Ernährungswissenschaft, Lehrstuhl Biochemie der Ernährung, Arthur-Scheunert-Allee 114-116, 14558 Bergholz-Rehbrücke, D-14558 Bergholz-Rehbrücke, Germany
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Eva ENGEMAIER;
Eva ENGEMAIER
Universität Potsdam, Institut für Ernährungswissenschaft, Lehrstuhl Biochemie der Ernährung, Arthur-Scheunert-Allee 114-116, 14558 Bergholz-Rehbrücke, D-14558 Bergholz-Rehbrücke, Germany
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Sina KOCH;
Sina KOCH
Universität Potsdam, Institut für Ernährungswissenschaft, Lehrstuhl Biochemie der Ernährung, Arthur-Scheunert-Allee 114-116, 14558 Bergholz-Rehbrücke, D-14558 Bergholz-Rehbrücke, Germany
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Ulrike BÖER;
Ulrike BÖER
Universität Potsdam, Institut für Ernährungswissenschaft, Lehrstuhl Biochemie der Ernährung, Arthur-Scheunert-Allee 114-116, 14558 Bergholz-Rehbrücke, D-14558 Bergholz-Rehbrücke, Germany
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Gerhard P. PÜSCHEL
Gerhard P. PÜSCHEL
2
Universität Potsdam, Institut für Ernährungswissenschaft, Lehrstuhl Biochemie der Ernährung, Arthur-Scheunert-Allee 114-116, 14558 Bergholz-Rehbrücke, D-14558 Bergholz-Rehbrücke, Germany
2To whom correspondence should be addressed (e-mail gpuesche@rz.uni-potsdam.de).
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Publisher: Portland Press Ltd
Received:
September 11 2002
Revision Received:
December 04 2002
Accepted:
January 08 2003
Accepted Manuscript online:
January 08 2003
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2003
2003
Biochem J (2003) 371 (2): 443–449.
Article history
Received:
September 11 2002
Revision Received:
December 04 2002
Accepted:
January 08 2003
Accepted Manuscript online:
January 08 2003
Citation
Frank NEUSCHÄFER-RUBE, Eva ENGEMAIER, Sina KOCH, Ulrike BÖER, Gerhard P. PÜSCHEL; Identification by site-directed mutagenesis of amino acids contributing to ligand-binding specificity or signal transduction properties of the human FP prostanoid receptor. Biochem J 15 April 2003; 371 (2): 443–449. doi: https://doi.org/10.1042/bj20021429
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