Supramolecular Architecture Of Rhodopsin Captured By The Afm Image And Available Crystallographic Data

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Based on the supramolecular architecture of rhodopsin captured by the AFM image and available crystallographic data, in 2003 the first model of higher order organization of a GPCR in its native membrane was derived implicating involvement of transmembrane domains in contact formation between neighboring rhodopsin molecules within the dimer as well as between distinct rows of dimers (Liang et al., 2003). This model suggested that the intradimeric contacts defining primary dimer interface involve transmembrane helices 4 (TM4) and 5 (TM5), whereas the formation of rhodopsin dimer rows is facilitated by the interaction between helices 1 (TM1) and 2 (TM2). Interestingly, a structure of squid rhodopsin, solved soon after, agreed with TM4/TM5 dimer very well (Murakami and Kouyama, 2008). Different experimental strategies have been further applied to identify rhodopsin dimer interface to validate this semi-empirical rhodopsin-packing model. Firstly, cysteine mutagenesis of specific amino acids predicted by molecular modeling to be involved in formation of the dimer-contacting surface followed by intermolecular crosslinking in the presence of cupric orthophenanthroline (CuP) let to the identification of two amino acids Trp175 and Tyr 206 at the dimer interface of opsin heterologously expressed in membranes of COS1 cells (Kota et al., 2006b). Trp175 is present in the extracellular loop connecting TM4 and TM5 and Tyr206 is located on the extracellular side of TM5 therefore

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