The Tie That Binds: Design of Biologically Active Single-Chain Human Chorionic Gonadotropins(2)

The availability of a three-dimensional structure permitted the results of previous studies on hCG using chemical modifications, synthetic peptides, limited proteolysis, protein engineering to produce hormone chimeras, and site-directed mutagenesis to be interpreted on a molecular basis. Also, the availability of a structure for the heterodimer has spawned many new investigations, with emphasis on site-directed mutagenesis and hormone chimeras, aimed at probing hor-mone-receptor contact sites. These findings have resulted in the identification of many amino acid residues on both subunits that appear to contribute to receptor interaction. While there is controversy and there are many gaps to be filled in, the data indicate that the middle portion and C-terminal region of a and the determinant loop of hCG(3, extending beyond Cys100, are important in receptor recognition and activation. levitra super active plus

The LHR cDNA established that the receptor is a member of the G protein-coupled receptor (GPCR) family and is characterized by a relatively large N-terminal extracellular domain (ECD) known to be responsible for high-af-finity ligand binding, seven transmembrane helices, three extracellular loops, three intracellular loops, and a С-terminal cytoplasmic tail. Numerous laboratories have been engaged in structure-function studies of LHR using site-directed mutagenesis and protein engineering for LHR chimeras. Structures are available for bacteriorhodopsin, a light-driven proton pump from Halobacterium halobium, and the visual pigment, (bovine) rhodopsin, but neither of these heptahelical receptors contains the large ECD of the glycoprotein hormone receptors.

This entry was posted in Gonadotropin and tagged Biologically Active Single-Chain Human, Chorionic Gonadotropins, Protein.