In silico insights into intra- and inter-species interactions of piscine gonadotropin hormones and receptor crosstalk

Ishwar Atre, Naama Mizrahi, Krist Hausken, Berta Levavi-Sivan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

In mammals, the gonadotropins follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are macromolecules secreted during specific reproductive phases and display strict specificity towards their cognate receptors. However, fish gonadotropins (GTH) and their receptors (GTHR) display diverse species-specific expression patterns, secretion patterns, and intra- and interspecies cross-activation. To uncover the molecular basis of this diversity, we generated and analyzed 29 in-silico models of intra- and inter-species combinations of sturgeon, carp, tilapia, and human gonadotropins with piscine receptors and analyzed the resulting receptor activation and signal transduction of these GTHR-GTH complexes in-vitro. Our results suggest that unlike humans, the surface charge on piscine FSH/LH β-seatbelt and N107huLHCGR/K104hFSHR homologs does not necessarily determine binding specificity. Instead, sequence and structural variations allow piscine GTHs significant conformational flexibility when binding to the receptor extracellular domain, thereby enabling cross-activation. The resulting diversity may support various reproductive strategies in different environmental niches.

Original languageAmerican English
Article number129524
JournalInternational Journal of Biological Macromolecules
Volume260
DOIs
StatePublished - Mar 2024

Bibliographical note

Publisher Copyright:
© 2024 The Authors

Keywords

  • Fish reproduction
  • GTH-GTHR complex
  • Gonadotropin crosstalk
  • Neuroendocrinology

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