Conservation of three-dimensional helix-loop-helix structure through the vertebrate lineage reopens the cold case of gonadotropin-releasing hormone-associated Peptide
Open accessAbstract
GnRH-associated peptide (GAP) is the C-terminal portion of the gonadotropin-releasing hormone (GnRH) preprohormone. Although it was reported in mammals that GAP may act as a prolactin-inhibiting factor and can be co-secreted with GnRH into the hypophyseal portal blood, GAP has been practically out of the research circuit for about 20 years. Comparative studies highlighted the low conservation of GAP primary amino acid sequences among vertebrates, contributing to consider that this peptide only participates in the folding or carrying process of GnRH. Considering that the three-dimensional (3D) structure of a protein may define its function, the aim of this study was to evaluate if GAP sequences and 3D structures are conserved in the vertebrate lineage. GAP sequences from various vertebrates were retrieved from databases. Analysis of primary amino acid sequence identity and similarity, molecular phylogeny, and prediction of 3D structures were performed. Amino acid sequence comparison and phylogeny analyses confirmed the large variation of GAP sequences throughout vertebrate radiation. In contrast, prediction of the 3D structure revealed a striking conservation of the 3D structure of GAP1 (GAP associated with the hypophysiotropic type 1 GnRH), despite low amino acid sequence conservation. This GAP1 peptide presented a typical helix-loop-helix (HLH) structure in all the vertebrate species analyzed. This HLH structure could also be predicted for GAP2 in some but not all vertebrate species and in none of the GAP3 analyzed. These results allowed us to infer that selective pressures have maintained GAP1 HLH structure throughout the vertebrate lineage. The conservation of the HLH motif, known to confer biological activity to various proteins, suggests that GAP1 peptides may exert some hypophysiotropic biological functions across vertebrate radiation.
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No conservation was found at the level of the C-terminal portion of propeptides, which in vertebrates contains the GnRH-associated peptide (GAP).
“In our sequence analysis, we found no conservation at the level of the C-terminal portion of propeptides, which in vertebrates contains the GnRH-associated peptide (GAP) (55, 56) (SI Appendix, Fig. S1).”
From Corazonin signaling integrates energy homeostasis and lunar phase to regulate aspects of growth and sexual maturation in <i>Platynereis</i> (2020) · cites this paper as [56]
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- Authors
- Pérez Sirkin, D. I., Lafont, A.-G., Kamech, N., Somoza, G. M., Vissio, P. G., & Dufour, S.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Consejo Nacional de Investigaciones Científicas y Técnicas (AR)
- Corresponding author
- Dufour, Sylvie
- Venue
- Frontiers in Endocrinology
- Publisher
- Frontiers Media SA
- Published
- 2017-08-22
- Volume
- 8
- Pages
- 207-207
- ISSN
- 1664-2392 (ISSN-L)
- PMC
- PMC5572233
- OpenAlex
- W2748892641
- Cited by
- 14
- References
- 72
- Citations by year
- 2026: 2 · 2022: 3 · 2021: 1 · 2020: 3 · 2019: 4 · 2018: 1
- FWCI
- 2.54
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Endocrinology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (publishedVersion, other-oa)
- HAL (submittedVersion, cc-by)
- Americanae (AECID Library) (submittedVersion, cc-by-nc-sa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Agence Nationale de la Recherche (ANR-14-CE02-0020)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Keywords
- vertebrate evolution, sequence conservation, molecular phylogeny, prolactin-inhibiting factor, selection pressure, structure-function relationship
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