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 combine d molecular genetic/biochemical approach. These studies led to the ide ntification of key residues on the receptors as well as the associated G proteins that are critically involved in determining proper recepto r/G protein recognition. Mutational analysis of the m3 muscarinic rece ptor showed that most native cysteine residues are not required for pr oductive receptor/G protein coupling. The putative extracellular disul fide bond was found to be essential for efficient trafficking of the r eceptor protein to the cell surface but not for receptor-mediated G pr otein activation. ((C)Elsevier, Paris).