The third transmembrane domains of the human B1 and B2 bradykinin receptor subtypes are involved in discriminating between subtype-selective ligands
(1997) In FASEB Journal 11(9). p.1327-1327- Abstract
The B1 and B2 bradykinin (BK) receptor subtypes belong to the GPCR faro ily, and they discriminate between peptides that differ only by the absence and presence of a C-terminal Arg, To identify receptor residues conferring tigand spe.cificity, chimeric constructs in which TM-III were exchanged between the receptors were expressed and assayed by radioligand binding and fluorescence Ca2+ imaging in t1EK293 and A10 cells, respectively. Substitution of B1 TMIII into the B2 receptor (B2(B1III) decreased the affinity for the B2-selective agonist BK and antagonist NPC17731, while substitution of B2 TM-III into the Bt receptor decreased the affinity for the Bl-selective agonist des-Argm-Lys BK. High affinity binding to B2(B1III) was fully... (More)
The B1 and B2 bradykinin (BK) receptor subtypes belong to the GPCR faro ily, and they discriminate between peptides that differ only by the absence and presence of a C-terminal Arg, To identify receptor residues conferring tigand spe.cificity, chimeric constructs in which TM-III were exchanged between the receptors were expressed and assayed by radioligand binding and fluorescence Ca2+ imaging in t1EK293 and A10 cells, respectively. Substitution of B1 TMIII into the B2 receptor (B2(B1III) decreased the affinity for the B2-selective agonist BK and antagonist NPC17731, while substitution of B2 TM-III into the Bt receptor decreased the affinity for the Bl-selective agonist des-Argm-Lys BK. High affinity binding to B2(B1III) was fully restored when one residue, Lys-11, in TMdlI was replaced with the corresponding residue, Serltl, in the wild-type B2 receptor. Binding was also restored by replacement with Ala, tlis, and Met, but not by' Arg. These results show that TM-III contributes significantly to the ability of these receptors to diseriminate between subtype selective ligands. We believe that the low affinity of B2-selective peptides for the B1 receptor is due in part to the positive charge of Lys-1. facing the ligand binding pocket which repels the positive charge of the C terminal Arg in these peptides.
(Less)
- author
- Fathy, D. B. ; Mathis, S. A. ; Leeb, T. and Leeb-Lundberg, I. M F LU
- publishing date
- 1997-12-01
- type
- Contribution to journal
- publication status
- published
- subject
- in
- FASEB Journal
- volume
- 11
- issue
- 9
- pages
- 1327 - 1327
- publisher
- Wiley
- external identifiers
-
- scopus:33750273257
- ISSN
- 0892-6638
- language
- English
- LU publication?
- no
- id
- 3777e063-ec02-408c-a916-ba0d4eb8b5d0
- date added to LUP
- 2019-06-10 11:09:06
- date last changed
- 2023-09-09 05:31:51
@article{3777e063-ec02-408c-a916-ba0d4eb8b5d0,
abstract = {{<p>The B1 and B2 bradykinin (BK) receptor subtypes belong to the GPCR faro ily, and they discriminate between peptides that differ only by the absence and presence of a C-terminal Arg, To identify receptor residues conferring tigand spe.cificity, chimeric constructs in which TM-III were exchanged between the receptors were expressed and assayed by radioligand binding and fluorescence Ca2+ imaging in t1EK293 and A10 cells, respectively. Substitution of B1 TMIII into the B2 receptor (B2(B1III) decreased the affinity for the B2-selective agonist BK and antagonist NPC17731, while substitution of B2 TM-III into the Bt receptor decreased the affinity for the Bl-selective agonist des-Argm-Lys BK. High affinity binding to B2(B1III) was fully restored when one residue, Lys-11, in TMdlI was replaced with the corresponding residue, Serltl, in the wild-type B2 receptor. Binding was also restored by replacement with Ala, tlis, and Met, but not by' Arg. These results show that TM-III contributes significantly to the ability of these receptors to diseriminate between subtype selective ligands. We believe that the low affinity of B2-selective peptides for the B1 receptor is due in part to the positive charge of Lys-1. facing the ligand binding pocket which repels the positive charge of the C terminal Arg in these peptides.</p>}},
author = {{Fathy, D. B. and Mathis, S. A. and Leeb, T. and Leeb-Lundberg, I. M F}},
issn = {{0892-6638}},
language = {{eng}},
month = {{12}},
number = {{9}},
pages = {{1327--1327}},
publisher = {{Wiley}},
series = {{FASEB Journal}},
title = {{The third transmembrane domains of the human B1 and B2 bradykinin receptor subtypes are involved in discriminating between subtype-selective ligands}},
volume = {{11}},
year = {{1997}},
}