Structural and Functional Role of Helices I and II in Rhodopsin (I)

We started a detailed characterization of adRP mutants in the transmembrane region of rhodopsin with a 2-fold interest, (i) elucidation of the molecular mechanism of the disease and (ii) structural and functional information, from the study of these mutations that might be relevant to other members of the GPCR superfamily. The rhodopsin crystal structure together with the available biochemical data on rhodopsin mutants has shed more light into the molecular mechanism of RP associated with rhodopsin mutations [Garriga and Manyosa, 2002; Stojanovic and Hwa, 2002]. Previous studies show that conservative mutations in helix III at Leu-125 (site of the adRP mutation L125R) led to misfolding, and it was proposed that the folding of the intradiscal and transmembrane domains are coupled [Liu et al., 1996a, Garriga et al., 1996, Hwa et al., 1997]. These studies were further extended to dissect the effect of mutations at Leu-125 in the folding and function of rhodopsin [Andrés et al., 2001].