NDLI: Role of group-conserved residues in the helical core of β2-adrenergic receptor

Content Provider	PubMed Central
Author	Chelikani, Prashen Hornak, Viktor Eilers, Markus Reeves, Phillip J. Smith, Steven O. Rajbhandary, Uttam L. Khorana, H. Gobind
Copyright Year	2007
Abstract	G protein-coupled receptors (GPCRs) belonging to class A contain several highly conserved (>90%) amino acids in their transmembrane helices. Results of mutational studies of these highly conserved residues suggest a common mechanism for locking GPCRs in an inactive conformation and for their subsequent activation upon ligand binding. Recently, a second set of sites in the transmembrane helices has been identified in which amino acids with small side chains, such as Gly, Ala, Ser, Thr, and Cys, are highly conserved (>90%) when considered as a group. These group-conserved residues have not been recognized as having essential structural or functional roles. To determine the role of group-conserved residues in the β2-adrenergic receptor (β2-AR), amino acid replacements guided by molecular modeling were carried out at key positions in transmembrane helices H2–H4. The most significant changes in receptor expression and activity were observed upon replacement of the amino acids Ser-161 and Ser-165 in H4. Substitution at these sites by larger residues lowered the expression and activity of the receptor but did not affect specific binding to the antagonist ligand dihydroalprenolol. A second site mutation, V114A, rescued the low expression of the S165V mutant. Substitution of other group-conserved residues in H2–H4 by larger amino acids lowered receptor activity in the order Ala-128, Ala-76, Ser-120, and Ala-78. Together these data provide comprehensive analysis of group-conserved residues in a class A GPCR and allow insights into the roles of these residues in GPCR structure and function.
Related Links	http://dx.doi.org/10.1073/pnas.0702024104
Ending Page	7032
Page Count	6
Starting Page	7027
File Format	PDF
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	17
Volume Number	104
Language	English
Publisher	National Academy of Sciences
Publisher Date	2007-04-24
Access Restriction	Open
Rights Holder	National Academy of Sciences
Subject Keyword	General Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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