Conservation of three-dimensional helix-loop-helix structure through the vertebrate lineage reopens the cold case of gonadotropin-releasing hormone-associated Peptide

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 o...

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Autores principales: Pérez Sirkin, D.I., Lafont, A.-G., Kamech, N., Somoza, G.M., Vissio, P.G., Dufour, S.
Formato: JOUR
Materias:
Evolution
GnRH-associated peptide
Helix-loop-helix
Phylogeny
Protein 3D structure
Teleosts
Vertebrates
Acceso en línea:http://hdl.handle.net/20.500.12110/paper_16642392_v8_nAUG_p207_PerezSirkin
Aporte de:
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires
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spelling todo:paper_16642392_v8_nAUG_p207_PerezSirkin2023-10-03T16:29:04Z Conservation of three-dimensional helix-loop-helix structure through the vertebrate lineage reopens the cold case of gonadotropin-releasing hormone-associated Peptide Pérez Sirkin, D.I. Lafont, A.-G. Kamech, N. Somoza, G.M. Vissio, P.G. Dufour, S. Evolution GnRH-associated peptide Helix-loop-helix Phylogeny Protein 3D structure Teleosts Vertebrates 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. © 2017 Pérez Sirkin, Lafont, Kamech, Somoza, Vissio and Dufour. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_16642392_v8_nAUG_p207_PerezSirkin
institution Universidad de Buenos Aires
institution_str I-28
repository_str R-134
collection Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic Evolution
GnRH-associated peptide
Helix-loop-helix
Phylogeny
Protein 3D structure
Teleosts
Vertebrates
spellingShingle Evolution
GnRH-associated peptide
Helix-loop-helix
Phylogeny
Protein 3D structure
Teleosts
Vertebrates
Pérez Sirkin, D.I.
Lafont, A.-G.
Kamech, N.
Somoza, G.M.
Vissio, P.G.
Dufour, S.
Conservation of three-dimensional helix-loop-helix structure through the vertebrate lineage reopens the cold case of gonadotropin-releasing hormone-associated Peptide
topic_facet Evolution
GnRH-associated peptide
Helix-loop-helix
Phylogeny
Protein 3D structure
Teleosts
Vertebrates
description 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. © 2017 Pérez Sirkin, Lafont, Kamech, Somoza, Vissio and Dufour.
format JOUR
author Pérez Sirkin, D.I.
Lafont, A.-G.
Kamech, N.
Somoza, G.M.
Vissio, P.G.
Dufour, S.
author_facet Pérez Sirkin, D.I.
Lafont, A.-G.
Kamech, N.
Somoza, G.M.
Vissio, P.G.
Dufour, S.
author_sort Pérez Sirkin, D.I.
title Conservation of three-dimensional helix-loop-helix structure through the vertebrate lineage reopens the cold case of gonadotropin-releasing hormone-associated Peptide
title_short Conservation of three-dimensional helix-loop-helix structure through the vertebrate lineage reopens the cold case of gonadotropin-releasing hormone-associated Peptide
title_full Conservation of three-dimensional helix-loop-helix structure through the vertebrate lineage reopens the cold case of gonadotropin-releasing hormone-associated Peptide
title_fullStr Conservation of three-dimensional helix-loop-helix structure through the vertebrate lineage reopens the cold case of gonadotropin-releasing hormone-associated Peptide
title_full_unstemmed Conservation of three-dimensional helix-loop-helix structure through the vertebrate lineage reopens the cold case of gonadotropin-releasing hormone-associated Peptide
title_sort conservation of three-dimensional helix-loop-helix structure through the vertebrate lineage reopens the cold case of gonadotropin-releasing hormone-associated peptide
url http://hdl.handle.net/20.500.12110/paper_16642392_v8_nAUG_p207_PerezSirkin
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