Structural studies of the putative helix 8 in the human beta(2) adrenergic receptor: an NMR study.
The recently reported crystal structure of bovine rhodopsin revealed a cytoplasmic helix (helix 8) in addition to the seven transmembrane helices. This domain is roughly perpendicular to the transmembrane bundle in the presence of an interface and may be a loop-like structure in the absence of an interface. Several studies carried out on this domain suggested that it might act as a conformational switch between the inactive and activated states of this G-protein coupled receptor (GPCR). These results raised the question whether helix 8 may be an important feature of other GPCRs as well. To explore this question, we determined the structure of a peptide representing the putative helix 8 domain in another receptor that belongs to the rhodopsin family of GPCRs, the human beta(2) adrenergic receptor (hbeta(2)AR), using two-dimensional (1)H nuclear magnetic resonance (NMR). The key results from this structural study are that the putative helix 8 domain is helical in detergent and in DMSO while in water this region is disordered; the conformation is therefore dependent upon the environment. Comparison of data from five GPCRs suggests that these observations may be generally important for GPCR structure and function.
Katragadda
M
M
Department of Molecular and Cell Biology, University of Connecticut, 91 North Eagleville Road, U-3125, Storrs, CT 06269-3125, USA.
Maciejewski
M W
MW
Yeagle
P L
PL
D000595:Amino Acid Sequence; D002942:Circular Dichroism; D006801:Humans; D008823:Micelles; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010767:Phosphorylcholine / Q000737:chemistry; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D018343:Receptors, Adrenergic, beta-2 / Q000737:chemistry* / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000235:genetics; D014867:Water / Q000737:chemistry
D008823:Micelles; D018343:Receptors, Adrenergic, beta-2; D043562:Receptors, G-Protein-Coupled; D014867:Water; D010767:Phosphorylcholine