Hormone interactions to Leu-rich repeats in the gonadotropin receptors - II. Analysis of Leu-rich repeat 4 of human luteinizing hormone/chorionic gonadotropin receptor

The luteinizing hormone receptor (LHR) consists of an similar to 350-amino acid-long N-terminal extracellular exodomain and a membrane-associated endo domain of similar size. Human chorionic gonadotropin (hCG) binds to the exo domain, and then hCG/exodomain complex is thought to make a secondary conta ct with the endodomain and generate hormone signals. The sequence alignment of the exodomain shows imperfectly matching eight to nine Leu-rich repeats (LRRs), In the preceding article (Song, Y., Ji, I., Beauchamp, J., Isaacs, N., and Ji, T, (2001) J. Biol. Chem. 276, 3426-3435), we have shown that L RR2 and LRR4 are crucial for hormone binding. In this work, we have examine d the residues of LRR4, in particular Leu(103) and Ile(105) in the putative beta strand. Our data show that Leu(103) and Ile(105) are involved in the specific, hydrophobic interaction of the LRR4 loop, likely to form the hydr ophobic core. This loop is crucial for the structural integrity of all of t he LRRs. In contrast, the downstream sequence consisting of Asn(107), Thr(1 08), Gly(109), and Ile(110) of LRR4 is crucial for cAMP induction but not f or hormone binding, folding, and surface expression. This implicates, for t he first time, its involvement in the interaction with the endodomain and s ignal generation. The evidence for the interaction is presented in the foll owing article.