3-DIMENSIONAL STRUCTURE OF THE CYTOPLASMIC FACE OF THE G-PROTEIN RECEPTOR RHODOPSIN

Rhodopsin is a G protein receptor from a many-membered family of membr ane receptors. No high-resolution structure exists for any member of t his family due to the insolubility of membrane proteins and the diffic ulty in crystallizing membrane proteins. Two new approaches to the str ucture of rhodopsin are described that circumvent these limitations: ( I) individual solution structures of the four cytoplasmic domains of r hodopsin are fitted with the transmembrane domain; (2) the solution st ructure of a complex of the four cytoplasmic domains is determined fro m nuclear magnetic resonance data. The two structures are similar. To test the validity of these structures, specific site-to-site distances measured on intact membrane-bound rhodopsin are compared to the same distances on the structures reported here. Excellent agreement is obta ined. Furthermore, the agreement is obtained with distances measured o n the activated form of the receptor and not with distances on the dar k-adapted form of rhodopsin. This approach may prove to have general a pplicability for the determination of the structure for membrane prote ins.