J. Rim et Dd. Oprian, CONSTITUTIVE ACTIVATION OF OPSIN - INTERACTION OF MUTANTS WITH RHODOPSIN KINASE AND ARRESTIN, Biochemistry, 34(37), 1995, pp. 11938-11945
Mutation of Gly(90), Glu(113), Ala(292), and Lys(296) in, the visual p
igment rhodopsin constitutively activates the protein for activation o
f the G protein transducin. Three of these mutations have been shown t
o cause two different human diseases. Mutation of Gly(90) and Ala(292)
results in complete night blindness, and mutation of Lys(296) results
in the degenerative disease retinitis pigmentosa. We show here that t
he mutants not only constitutively activate transducin but are also co
nstitutively activated for phosphorylation by rhodopsin kinase. In add
ition, the phosphorylated mutants are shown to bind tightly to the inh
ibitory protein arrestin in a reaction that quenches the activity towa
rd transducin. Thus the same mutations that result in constitutive act
ivation of transducin also result in constitutive phosphorylation by r
hodopsin kinase and binding of-arrestin to inhibit the activity. This
implies that the same conformational change may be responsible for act
ivation of transducin and rhodopsin kinase. It also suggests that dege
neration of photoreceptor cells in retinitis pigmentosa results indire
ctly from the activated state of the receptor, perhaps as a consequenc
e of phosphorylation and persistent binding of arrestin.