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The role of N-terminal and C-terminal Arg residues from BK on interaction with kinin B2 receptor
- Source :
- Biological Chemistry. 397:305-314
- Publication Year :
- 2016
- Publisher :
- Walter de Gruyter GmbH, 2016.
-
Abstract
- Bradykinin (BK) is a nonapeptide important for several physiological processes such as vasodilatation, increase in vascular permeability and release of inflammatory mediators. BK performs its actions by coupling to and activating the B2 receptor, a family A G-protein coupled receptor. Using a strategy which allows systematical monitoring of BK R1 and R9 residues and B2 receptor acidic residues Glu5.35(226) and Asp6.58(298), our study aims at clarifying the BK interaction profile with the B2 receptor [receptor residue numbers are normalized according to Ballesteros and Weinstein, Methods Neurosci. 25 (1995), pp. 366–428) followed by receptor sequence numbering in brackets]. N- and C-terminal analogs of BK (-A1, -G1, -K1, -E1 and BK-A9) were tested against wild type B2, Glu5.35(226)Ala and Asp6.58(298)Ala B2 mutant receptors for their affinity and capability to elicit responses by mechanical recordings of isolated mice stomach fundus, measuring intracellular calcium mobilization, and competitive fluorimetric binding assays. BK showed 2- and 15-fold decreased potency for Glu5.35(226) and Asp6.58(298) B2 mutant receptors, respectively. In B2-Glu5.35(226)Ala BK analogs showed milder reduction in evaluated parameters. On the other hand, in the B2-Asp6.58(298)Ala mutant, no N-terminal analog was able to elicit any response. However, the BK-A9 analog presented higher affinity parameters than BK in the latter mutant. These findings provide enough support for defining a novel interaction role of BK-R9 and Asp6.58(298) receptor residues.
- Subjects :
- 0301 basic medicine
Receptor, Bradykinin B2
Arginine
Clinical Biochemistry
Mutant
Bradykinin
CHO Cells
Biochemistry
Mice
03 medical and health sciences
chemistry.chemical_compound
Cricetulus
Animals
Bradykinin receptor
Receptor
Molecular Biology
Cells, Cultured
030102 biochemistry & molecular biology
biology
Wild type
Kinin
biology.organism_classification
Molecular biology
Mice, Inbred C57BL
030104 developmental biology
chemistry
Mutation
Subjects
Details
- ISSN :
- 14374315 and 14316730
- Volume :
- 397
- Database :
- OpenAIRE
- Journal :
- Biological Chemistry
- Accession number :
- edsair.doi.dedup.....ab4cf4455f57ceeb3f83c4a2942e7785