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bioRxiv · 10.64898/2026.08.28.747697

From neuropeptide and receptor annotation to ligand-receptor pairing: a sequence- and structure-based framework for mapping the neuropeptide-receptor interactome in Gryllus bimaculatus

Margaretha, F.·Sakamoto, M.·Seike, H.·Nagata, S.·Nakamura, Y.·Mochizuki, T.
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Abstract

Neuropeptides and their G protein-coupled receptors (GPCRs) control much of insect physiology and behaviour, but in Gryllus bimaculatus, an emerging model and edible insect, receptor sequence similarity hinders the mapping of which peptide each GPCR activates. We re-annotated a chromosome-scale genome (BUSCO 95.3%, from 86.7% on insecta_odb12) with comprehensive curation of 48 neuropeptide precursor families (51 loci, including seven not previously identified) and 134 candidate GPCRs (66 rhodopsin-class, 68 secretin-class), providing a near complete neuropeptide-receptor interactome catalogue. We modelled all 15,946 peptide-receptor pairs with AlphaFold3 and Boltz-2 and scored each interface with pLDDT and ipSAE. Ranking these scores, and cross-checking the top candidate for each family against a receptor phylogeny of known ligand specificity, gave a confident, phylogenetically related receptor for 27 of 35 curated receptor groups. These matches confirm the structural scorings with existing deorphanization data and propose receptors for peptides with no prior functional evidence. The annotation, curated peptide and receptor sets, and ranked complexes are available through CricketBase (https://cricket.annotation.jp), a genome browser with a structure viewer of peptide-receptor complexes, providing a resource for G. bimaculatus endocrinology and a workflow to deorphanize GPCRs in other non-model insects.

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Margaretha, F., Sakamoto, M., Seike, H., Nagata, S., Nakamura, Y., Mochizuki, T.. 2026-09-03. From neuropeptide and receptor annotation to ligand-receptor pairing: a sequence- and structure-based framework for mapping the neuropeptide-receptor interactome in Gryllus bimaculatus. https://doi.org/10.64898/2026.08.28.747697

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