Extracellular cysteines

Data from studies with other GPCRs have highlighted the importance of extracellular cysteines in ligand binding and the maintenance of the conformational integrity of the receptors. There are typically four conserved cysteine residues found on extracellular domains of chemokine receptors (see Figure 1 and Tables 2 and 3) one on the amino-terminus and one on each of the three extracellular loops. It is clear that the cysteines on extracellular loops 1 and 2 form a disulfide bond that is essential for the proper trafficking of the receptors... 

Blanpain C, Lee B, Vakili J, et al. Extracellular cysteines of CCR5 are required for chemokine binding, but dispensable for HIV-1 coreceptor activity. J Biol Chem 1999 274(27) 18902-18908. 

Elliott, C., Muller, J., Miklis, M., Bhat, R. A., Schulze-Lefert, P. and Panstruga, R. (2005). Conserved extracellular cysteine residues and cytoplasmic loop-loop interplay are required for functionality of the heptahe-lical MLO protein. Biochem J. 385, 243-54. 

Bl. Baici, A., Gyger-Marazzi, M., and Strauli, P., Extracellular cysteine proteinase and col-lagenase activities as a consequence of tumor-host interaction in the rabbit V2 carcinoma. Invasion Metastasis 4, 13-27 (1984). 

DingZ, Kim S, Dorsam RT Jin J, Kunapuli SR Inactivation ofthe human P2YI2 receptor by thiol reagents requires interaction with both extracellular cysteine residues, Cysl7 and Cys270, Blood 2003 101 3908-3914. 

The distances from the intracellular eGFP to the extracellular cysteines in the S1-S2 and S3-S4 loops were large but they showed very little voltage dependence. Some increased with depolarization and others decreased, but the changes were never larger than 2 A. These results do not support a large translation of S4 perpendicular to the membrane. 

Ai, L. S., and Liao, F. (2002). Mutating the four extracellular cysteines in the chemo-kine receptor CCR6 reveals their differing roles in receptor trafficking, ligand binding, and signaling. Biochem. 41, 8332-8341. 

Mihm, S., Gaiter, D., and Droge, W. (1995). Modulation of transcription factor NF kappa B activity hy intracellular glutathione levels and hy variations of the extracellular cysteine supply. FASEB J 9, 246-52. 

D. Neumann, D. Barchen, M. Horowitz, E. Kochva, and S. Fuchs Snake acetylcholine receptor Cloning of the domain containing the four extracellular cysteines of the alpha-subunit. 1989. Proc. Natl. Acad. Sci. USA 86, 7255-7259. 

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