z-logo
Premium
Bradykinin B2 receptor signaling: Structural and functional characterization of the C‐terminus
Author(s) -
Piserchio Andrea,
Zelesky Veronica,
Yu Jun,
Taylor Linda,
Polgar Peter,
Mierke Dale F.
Publication year - 2005
Publication title -
peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.20220
Subject(s) - g protein coupled receptor , chemistry , receptor , rhodopsin , helix (gastropod) , signal transduction , mutant , bradykinin , biochemistry , stereochemistry , inositol phosphate , biophysics , inositol , biology , retinal , ecology , snail , gene
Over the last few years the importance of the intracellular C‐terminus in the signaling of G‐protein coupled receptors (GPCR) has become increasingly evident. In an effort to provide a structural framework for biological function, we have determined the conformation of the C‐terminus of the bradykinin (BK) B2 receptor. Using a uniformly 15 N‐ and 13 C‐enriched sample of the BKB2 receptor [309–366], NMR results clearly define three α‐helices lying on the zwitterionic surface of the dodecylphosphocholine. The proximal helix consisting of residues 311–326 was previously predicted based on homology modeling with rhodopsin. This corresponds to what is often called helix‐8 of the GPCRs. The two distal helices, residues 333–345 and 348–363, are clearly borne out by the NMR data. The functional importance of these secondary structural elements was probed by determination of the signaling properties (inositol phosphate formation) of mutant BKB2 receptors lacking the domains (deletion mutants) or containing the corresponding region from the related GPCR, angiotensin II AT1a (chimera receptors). We demonstrate that the regions between the helices (residues 327–333 and 346–347) can be exchanged without loss of signaling. In contrast, modification of the three helices, particularly the hydroxyl‐containing residues, has drastic effects on the signaling profile of the BKB2 receptor. By coupling of the structural features with the functional data, the molecular mechanisms of signaling by the BKB2 receptor are beginning to be established.© 2005 Wiley Periodicals, Inc. Biopolymers (Pept Sci), 2005

This content is not available in your region!

Continue researching here.

Having issues? You can contact us here