Structure-function analysis of muscarinic acetylcholine receptors.
The structural basis underlying the G protein coupling selectivity of different muscarinic receptor subtypes was analyzed by using a combined molecular genetic/biochemical approach. These studies led to the identification of key residues on the receptors as well as the associated G proteins that are critically involved in determining proper receptor/G protein recognition. Mutational analysis of the m3 muscarinic receptor showed that most native cysteine residues are not required for productive receptor/G protein coupling. The putative extracellular disulfide bond was found to be essential for efficient trafficking of the receptor protein to the cell surface but not for receptor-mediated G protein activation.
Kostenis
E
E
Laboratory of Bioorganic Chemistry, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA.
Zeng
F Y
FY
Wess
J
J
D000595:Amino Acid Sequence; D000818:Animals; D003545:Cysteine / Q000737:chemistry; D019204:GTP-Binding Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D016296:Mutagenesis; D011976:Receptors, Muscarinic / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology; D013329:Structure-Activity Relationship
D011976:Receptors, Muscarinic; D019204:GTP-Binding Proteins; D003545:Cysteine