Considering the effect of luteinizing hormone receptor (LHR) polymorphisms (LHR) on their binding affinity to LH in dairy cow with docking method

Luteinizing hormone (LH) is one of the most important reproductive hormones that is secreted by the anterior pituitary gland and plays a key role in regulating the estrous cycle, maturation of ovarian follicles, ovulation, corpus luteum formation, corpus luteum development and maintenance. The LH message is transmitted through by binding it to its extracellular receptors, so that after binding to its own receptor (LHR), LH activates the intracellular cascade chain by activating the secondary messenger cAMP, and ultimately the expression of specific proteins and enzymes. Therefore, the interaction of luteinizing hormone (LH) with its specific receptor (LHR) is one of the key steps in the path of follicular maturation and ovulation. Polymorphisms and LHR splicing are among the genetic changes that can affect LH function and consequent reproductive efficiency.The aim of this study was to compare the tertiary structure of different LHR polymorphisms and their binding affinity to LH in dairy cows.

For this purpose, LHR amino acid sequences were obtained from Gene bank. Firstly, Polymorphisms were identified by alignment analysis. Their related third structures were predicted by homology modeling technique using Modeller software. The created structures were observed and evaluated using PyMol 2.5.1 graphics software and Ramachandran plot. Also, different physico-chemical parameters of the modeled proteins such as isoelectric point, molecular weight, and number of negative and positive sequences and Grand Average of hydropathicity (GRAVY) were calculated using ProtParam tool in Expasy database. Then, the affinity of LH to each of the LHR polymorphism was evaluated using molecular docking technique based on binding energy and spatial position indices.

Based on the results, only two polymorphisms (LHR1 and LHR2) were identified among the studied sequences. The predicted models for the two polymorphisms have a good quality and there was no difference in structural and physicochemical parameters between them. Docking results showed that, despite the difference in total binding energy between the two polymorphisms, this difference could not be attributed to amino acid substitution and this difference is probably related to an orientation of the LH relative to the LHR1 and LHR2. Most of the amino acids that were involved in hydrogen bonding were similar in both the LH-LHR1 and LH-LHR2 complexes.

In general, the results of this study can be used to the relationship between LHR polymorphism and its physiological activity.