Rhodopsin, structure

Since the activation mechanism likely involves displacements of transmembrane helices relative to one another, the helix contacts illuminated by the crystal structure provide a wealth of new information relevant to rhodopsin mechanism. For example, the tilt and central location of TMlll indicates that it can pack against and articulate with TMll and VI, while TMVl is significantly kinked by the presence of Pro267 ° near its extracellular end. These helical interfaces and proline-induced kinks comprise important aspects of current hypotheses of receptor activation (HubbeU et al, 2003 Visiers et al, 2002). Interestingly, TMs 1, IV, and V also contain conserved prolines but are not kinked significantly. The extracellular loops and amino terminus were found to contain antiparaUel / strands, with a strand provided by ECLlf partially buried in the central pore where 

Numerous insightful reviews detail the use of the rhodopsin crystal structure as a model building template for other class A GPCRs (Archer et al., 2003 Ballesteros et al., 2001 Becker et al., 2003 FUipek et al, 2003). Modeling studies of GPCR structure have been advanced to such an extent that ab initio structure prediction methods using the minimum possible experimental structural information are underway (Vaidehi et al., 2002). 

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Meng, E. C. and Bourne, H. R. (2001) Receptor activation what does the rhodopsin structure tell us Trends Pharmacol. Sci. 22, 587-593. 

Lucas RJ, Douglas RH, Foster RG 2001 Characterization of an ocular photopigment capable of driving pupillary constriction in mice. Nat Neurosci 4 621—626 Lythgoe JN, Shand J, Foster RG 1984 Visual pigment in fish iridocytes. Nature 308 83—84 Menon ST, Han M, Sakmar TP 2001 Rhodopsin structural basis of molecular physiology. Physiol Rev 81 1659-1688... 

Menon, S.T., Han, M., Sakmar, T.P. (2001) Rhodopsin structural basis of molecular physiology. Physiol. Rev. 81, 1659-1688. Advanced review. 

Nathans, J., Rhodopsin Structure, function and genetics. Biochemistry 31 4923, 1992. A review of recent work on the structure and reactions of rhodopsin. 

Hubbell, W. L., Altenbach, C., Hubbell, C. M., and Khorana, H. G. (2003). Rhodopsin structure, dynamics, and activation A perspective from crystallography, site-directed spin labeling, sulfhydryl reactivity, and disulfide cross-linking. Adv. Protein Chem. 63, 243-290. 

One of the most striking features of the rhodopsin structure is the complexity and compactness of a helix bundle cap or plug formed from the extracellular interhelix loops and N-terminal segment (19). Together, the N-terminal... 

The rhodopsin structure places the il loop adjacent to the short eighth membrane-embedded a-helix. With the exception of the 5-HT4A receptor (six residues), the 5-HT receptors have the same length as the rhodopsin loop (seven residues). Interestingly a XKKLXXX motif is conserved between the rhodopsin sequence and the majority of the 5-HT sequences, suggesting that the il loops of rhodopsin and the 5-HT receptors could have a common structure. Systematic mutagenesis studies have not been conducted. 

The rhodopsin structure shows a helix irregularity in the extracellular half of TM2, placing it toward TM1, which is initiated by a pair of glycine residues... 

I. Nathans. Rhodopsin structure, function and genetics. Biochemistry 33 4931-4936... 

Fig. 17A (see color insert) shows a ribbon model of the rhodopsin structure indicating the residues assigned to the interface in each helix by a sphere centered on the corresponding of-carbon. Also shown is a sphere on the a-carbon of residue 314, which is located in the interface (see Section III,F). Clearly, these residues define a unique plane of intersection of the molecule with the membrane-aqueous interface. The shaded band in Fig. 17 represents a phospholipid bilayer with a phosphate-phosphate distance of 40 A, the expected thickness of the bilayer in the disk membrane (Saiz and Klein, 2001). The outer interface of the bilayer is positioned so that the polar head groups coincide with the intersection plane defined by the data in Fig. 16. This procedure then fixes the intersection plane of the molecule on the extracellular surface as well.

The position of rhodopsin in the membrane deduced from SDSL data is compatible with the topography of surface residues in the molecule. Figure 17B shows a space-filling model of the rhodopsin structure with residues color coded according to charge, polarity, and identity of tyrosines and tryptophans. It is clear that the demarcation between the charged and hydrophobic residues on the cytoplasmic surface defines... 

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