Figure 7.

Sketches of the different hLH and hCG interactions with the middle section of the hinge region with various LHCGR constructs. (A) LHCGR-wt: exon10-helix shifts the sulfated sTyr331 into an appropriate spatial position necessary to interact with hLH, while, for hCG, exon10-helix acts as a structural interface. (B) LHCGR-delExon10: deletion of exon 10 leads to displacement of the remaining residues beyond the cutting point (red triangle). Subsequently sTyr331 abrogates the interaction with hLH, However, the adjacent helix moves into the position previously occupied by the exon 10-helix and thus provides a structural interface for activation by hCG; (C) LHCGR-Q303P/E308P double proline mutation within exon10 disturbs the helical structure of exon10-helix and interferes with the hCG-induced hinge movement and signaling. However, in this case, the retained length of the middle hinge region allows the appropriate adjustment of sTyr331 for proper hLH interaction and signaling.