Publicado

2020-08-25

MODELLING OF 3D-STRUCTURES OF THE RARE MELANOCORTIN-1-RECEPTOR MUTATIONS ASSOCIATED TO MELANISM IN THE BANANAQUIT

MODELADO DE ESTRUCTURAS-3D DE MUTACIONES RARAS DEL RECEPTOR-1-MELANOCORTINA ASOCIADAS AL MELANISMO EN EL MIELERO

MODELAGEM DE ESTRUTURAS-3D DE MUTAÇÕES RARAS DO RECEPTOR-1-MELANOCORTINA ASSOCIADAS AO MELANISMO NO MIELERO

DOI:

https://doi.org/10.15446/abc.v26n1.81432

Palabras clave:

Birds, Eumelanin, E92K, Protein Evolution, 3D-folding (en)
Aves, Eumelanina, Evolución de Proteínas, E92K, Torción-3D (es)
Pássaros, Eumelanina, Evolução de Proteínas, E92K, Torción-3D (pt)

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Autores/as

Melanism in plumage color is often associated to the single nucleotide polymorphism of the melanocortin-1-receptor (MC1R). Despite the striking association between the substitution of a Glutamic-acid by for a Lysine at position 92 on the MC1R protein and a completely black plumage, an in-depth understanding of the effect of missense mutations on the conformational change and behavior of the MC1R in the lipid bilayer caused by the absence of a crystal structure is lacking. We examine the structural basis for receptor activation using DNA sequences from the GenBank to perform in silicoprotein homology-based modeling. Our tridimensional model shows that the Alanine for a 179-Threoninesubstitution is a structural complement of the charge-reversing effect associated to the substitution of a Glutamic-acid by for a Lysine at position 92 on the MC1R. We proposed the possibility of gradual evolution in stability and electrostatic properties of the MC1R by the sequential accumulation of these two rare substitutions. These two rare substitutions further perturb physical-chemical properties that may be necessary folding requirements of the constitutively active MC1R forms without altering of ligand binding affinity. The computational coarse-grained molecular dynamics of the MC1R binding affinities to the melanocyte-stimulating hormone predicted the disparity in ligand binding amongalleles. We speculate that the disparity in structural constraints and ligand binding among the alleles within heterozygous individuals may contribute as a mechanism to the plumage color variation in the Coereba flaveola.

El melanismo en el color del plumaje se asocia frecuentemente al polimorfismo del receptor melanocortina-1(MC1R). La ausencia de una estructura cristalográfica de la asociación entre la sustitución del Glutamato por Lisina en la posición 92 de la proteína MC1R y el plumaje completamente negro, no ha permitido tener un mejor entendimiento del efecto de mutaciones no sinónimas en la conformación y en el comportamiento en la membrana del MC1R. Examinamos la estructura asociada a la activación del receptor usando secuencias de ADN obtenidas del GenBank, para un modelamiento in silicode formas homólogas de la proteína. El modelo tridimensional muestra que la sustitución de Alanina por la Treonina en la posición 179 es un complemento estructural al efecto de reversión de carga asociado a la sustitución del Glutamato por Lisina en la posición 92 del MC1R. Proponemos la posibilidad de evolución gradual de la estabilidad y de propiedades electrostáticas del MC1R por la acumulación de estas substituciones. Estas perturban las propiedades fisicoquímicas que podrían ser necesarias para el plegamiento de las formas constitutivamente activas del MC1R sin alterar la afinidad de empalme con el ligando. La modelación computacional de la dinámica molecular de la afinidad de empalme del MC1R a la hormona estimulante de meloncitos predice la disparidad de la unión con el ligando entre alelos. Consideramos que posiblemente la disparidad entre alelos en heterocigotos en cuanto a restricciones estructurales y la unión con el ligando podría contribuir a la variación en el color del plumaje en Coereba flaveola.

O melanismo da cor da plumagem é frequentemente associado ao polimorfismo do gene do receptor da melanocortina-1 (MC1R). A partir da associação entre a substituição do glutamato por lisina na posição 92 da proteína MC1R e a plumagem completamente preta, ainda há uma melhor compreensão do efeito de mutações não-sinônimas na conformação e comportamento da membrana do MC1R devido à ausência de glutamato. uma estrutura cristalográfica. Examinamos a estrutura associada à ativação do receptor usando seqüências de DNA obtidas do GenBank, para modelagem in silico de formas homólogas da proteína. O modelo tridimensional mostra que a substituição de alanina por treonina na posição 179 é um complemento estrutural do efeito da inversão de carga associada à substituição do glutamato pela lisina na posição 92 do MC1R. Propomos a possibilidade de evolução gradual da estabilidade e propriedades eletrostáticas do MC1R pelo acúmulo dessas substituições, que perturbam as propriedades físico-químicas que podem ser necessárias para a duplicação das formas constitutivamente ativas do MC1R sem alterar a afinidade do splicing com o ligante . A modelagem computacional da dinâmica molecular da afinidade do splicing do MC1R com o hormônio estimulante do melão estimula a disparidade de ligação com o ligante entre os alelos. Acreditamos que possivelmente a disparidade entre alelos em heterozigotos em termos de restrições estruturais e ligação com o ligante possa contribuir para a variação na cor da plumagem em Coereba flaveola.

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APA

Sedano-Cruz, R. E. y Osorio, D. C. (2020). MODELLING OF 3D-STRUCTURES OF THE RARE MELANOCORTIN-1-RECEPTOR MUTATIONS ASSOCIATED TO MELANISM IN THE BANANAQUIT. Acta Biológica Colombiana, 26(1), 30–41. https://doi.org/10.15446/abc.v26n1.81432

ACM

[1]
Sedano-Cruz, R.E. y Osorio, D.C. 2020. MODELLING OF 3D-STRUCTURES OF THE RARE MELANOCORTIN-1-RECEPTOR MUTATIONS ASSOCIATED TO MELANISM IN THE BANANAQUIT. Acta Biológica Colombiana. 26, 1 (dic. 2020), 30–41. DOI:https://doi.org/10.15446/abc.v26n1.81432.

ACS

(1)
Sedano-Cruz, R. E.; Osorio, D. C. MODELLING OF 3D-STRUCTURES OF THE RARE MELANOCORTIN-1-RECEPTOR MUTATIONS ASSOCIATED TO MELANISM IN THE BANANAQUIT. Acta biol. Colomb. 2020, 26, 30-41.

ABNT

SEDANO-CRUZ, R. E.; OSORIO, D. C. MODELLING OF 3D-STRUCTURES OF THE RARE MELANOCORTIN-1-RECEPTOR MUTATIONS ASSOCIATED TO MELANISM IN THE BANANAQUIT. Acta Biológica Colombiana, [S. l.], v. 26, n. 1, p. 30–41, 2020. DOI: 10.15446/abc.v26n1.81432. Disponível em: https://revistas.unal.edu.co/index.php/actabiol/article/view/81432. Acesso em: 3 ago. 2024.

Chicago

Sedano-Cruz, Raúl Ernesto, y Daniel Camilo Osorio. 2020. «MODELLING OF 3D-STRUCTURES OF THE RARE MELANOCORTIN-1-RECEPTOR MUTATIONS ASSOCIATED TO MELANISM IN THE BANANAQUIT». Acta Biológica Colombiana 26 (1):30-41. https://doi.org/10.15446/abc.v26n1.81432.

Harvard

Sedano-Cruz, R. E. y Osorio, D. C. (2020) «MODELLING OF 3D-STRUCTURES OF THE RARE MELANOCORTIN-1-RECEPTOR MUTATIONS ASSOCIATED TO MELANISM IN THE BANANAQUIT», Acta Biológica Colombiana, 26(1), pp. 30–41. doi: 10.15446/abc.v26n1.81432.

IEEE

[1]
R. E. Sedano-Cruz y D. C. Osorio, «MODELLING OF 3D-STRUCTURES OF THE RARE MELANOCORTIN-1-RECEPTOR MUTATIONS ASSOCIATED TO MELANISM IN THE BANANAQUIT», Acta biol. Colomb., vol. 26, n.º 1, pp. 30–41, dic. 2020.

MLA

Sedano-Cruz, R. E., y D. C. Osorio. «MODELLING OF 3D-STRUCTURES OF THE RARE MELANOCORTIN-1-RECEPTOR MUTATIONS ASSOCIATED TO MELANISM IN THE BANANAQUIT». Acta Biológica Colombiana, vol. 26, n.º 1, diciembre de 2020, pp. 30-41, doi:10.15446/abc.v26n1.81432.

Turabian

Sedano-Cruz, Raúl Ernesto, y Daniel Camilo Osorio. «MODELLING OF 3D-STRUCTURES OF THE RARE MELANOCORTIN-1-RECEPTOR MUTATIONS ASSOCIATED TO MELANISM IN THE BANANAQUIT». Acta Biológica Colombiana 26, no. 1 (diciembre 28, 2020): 30–41. Accedido agosto 3, 2024. https://revistas.unal.edu.co/index.php/actabiol/article/view/81432.

Vancouver

1.
Sedano-Cruz RE, Osorio DC. MODELLING OF 3D-STRUCTURES OF THE RARE MELANOCORTIN-1-RECEPTOR MUTATIONS ASSOCIATED TO MELANISM IN THE BANANAQUIT. Acta biol. Colomb. [Internet]. 28 de diciembre de 2020 [citado 3 de agosto de 2024];26(1):30-41. Disponible en: https://revistas.unal.edu.co/index.php/actabiol/article/view/81432

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