Characteristics of neurokinin-3 receptor and its binding sites by mutational analysis

Ishwar Atre, Naama Mizrahi, Berta Levavi-Sivan

Research output: Contribution to journalArticlepeer-review

Abstract

NKB (Neurokinin B) is already known to play a crucial role in fish reproduction, but little is known about the structure and function of NKB receptors. Based on an in silico model of the tilapia NKB receptor Tachykinin 3 receptor a (tiTac3Ra) found in the current study, we determined the key residues involved in binding to tilapia NKB and its functional homologue NKF (Neurokinin F). Despite studies in humans suggesting the crucial role of F2516.44 and M2897.43 in NKB binding, no direct peptide interaction was observed in tilapia homologs. In-silico, Ala mutations on residues F2516.44 and M2897.43 did not influence binding affinity, but significantly affected the stability of tiTac3Ra. Moreover, in vitro studies indicated them to be critical to tiNKB/tiNKF-induced receptor activity. The binding of NKB antagonists to tiTac3Ra both in-vitro and in vivo inhibits FSH (follicle stimulating hormone) and LH (luteinizing hormone) release and sperm production in mature tilapia males. Non-peptide NKB antagonist SB-222200 had a strong inhibitory effect on the Tac3Ra activation. SB-222200 also decreased LH plasma levels; two hours post intraperitoneal injection, changed sperm volume and the ratios of the different stages along the spermatogenesis in tilapia testes.

Original languageAmerican English
Article number968
JournalBiology
Volume10
Issue number10
DOIs
StatePublished - 27 Sep 2021

Keywords

  • CRE luciferase assay
  • Molecular docking
  • Neurokinin B
  • Neurokinin F
  • Neuropeptides
  • Nonpeptide tachykinin receptor antagonist
  • Spermatogenesis
  • Tac3Ra
  • Tachykinin receptors
  • Tilapias

All Science Journal Classification (ASJC) codes

  • General Immunology and Microbiology
  • General Biochemistry,Genetics and Molecular Biology
  • General Agricultural and Biological Sciences

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