The Tie That Binds: Design of Biologically Active Single-Chain Human Chorionic Gonadotropins(1)

Chain Human Chorionic Gonadotropins(1)

Recent major advances in the elucidation of structure-function relationships of the gonadotropins, hCG and LH, and their common receptor (LHR) include determination of the crystal structure of hydrogen fluoride (HF)-treated hCG, characterization of LHR cDNAs from several species (cf. for review), and determination of the genomic organization of the LHR gene. Coupled with the results of earlier and more recent gonadotropin/receptor investigations, these breakthroughs have placed the field on a firm molecular foundation and have opened up numerous new avenues of study. ventolin inhaler

The crystal structure of HF-treated hCG revealed many surprises: the holoprotein is quite asymmetrical with loops of the a and (3 subunits intertwined to form a relatively large subunit-subunit contact surface; the a and (3 subunits have similar folding patterns, although there is no significant homology in their amino acid sequences; a cystine-knot motif, consisting of three disulfides, is present in each subunit and is similar to that observed in several growth factors; and a portion of the fj subunit, consisting of amino acid residues 90-110, wraps over the a subunit forming what has been termed a seat belt (Fig. la). This latter observation is of particular interest when compared with the results on the kinetics and pathway of hCG|3 folding and its association with a. It was found that several of the disulfides form in hCGp, followed by association with a; finally closure of the hCGp 26-110 disulfide locks the seat belt into place and stabilizes the holoprotein.

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