From the observation that much of the ECD of LHR is composed of pseudoleucine-rich repeats, several groups have modeled this region of the receptor with the structure of the leucine-rich repeat protein, porcine ribo-nuclease inhibitor, as a template. The resulting models exhibit a cusp-shaped structure, although there are specific differences in several of the proposed folding patterns, attributable in large part to the number of leucine-rich repeats chosen. Figure lb shows a model based on nine leucine-rich repeats developed by our laboratory in collaboration with Drs. Lapthom and Isaacs.
Based on an analysis of over 200 GPCRs, Baldwin proposed an organization of the transmembrane helices (TMH), complementing the low-resolution structural data on bacteriorhodopsin and bovine rhodopsin (Fig. lc). Presently, there are no structural data or models of the six loops or the С-terminal cytoplasmic tail. Buy Asthma Inhalers Online
The results of mutagenesis studies have been highly revealing in identifying amino acid residues and regions of LHR that are important in ligand binding. Of particular interest are the recent observations of LHR residues that appear to be involved in the transmembrane signaling cascade, but not in ligand binding; elucidation of these regions may provide valuable information on the mechanism of receptor activation.
FIG. 1. a) Ribbon diagram of the structure of HF-treated hCC showing the polypeptide backbones only of the a and p subunits. (The electron densities for amino acid residues 1-4 and 90-92 of a and those of 1 and 112-145 of fS could not be determined, presumably because of the flexible nature of these regions, and thus are not shown; nor are the carbohydrate locations given.) The seat belt is indicated by the arrows, b) Model of a portion of the ECD of LHR based on nine leucine-rich repeats; the N-terminal region and the portion of the ECD upstream of TMH 1 have not been modeled (modified from ). c) Organization of the seven TMHs in GPCRs.