Evolutionary and Functional Relationships in the Truncated Hemoglobin Family

Predicting function from sequence is an important goal in current biological research, and although, broad functional assignment is possible when a protein is assigned to a family, predicting functional specificity with accuracy is not straightforward. If function is provided by key structural prope...

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Autores principales:	Bustamante, J.P., Radusky, L., Boechi, L., Estrin, D.A., ten Have, A., Martí, M.A.
Formato:	JOUR
Materias:	truncated hemoglobin oxygen amino acid sequence Article binding site computer model controlled study evolutionary adaptation molecular evolution molecular model oxygen affinity phylogenetic tree protein binding protein folding protein function structure activity relation biology chemistry genetics metabolism molecular genetics phylogeny physiology sequence alignment statistical model Amino Acid Sequence Computational Biology Evolution, Molecular Linear Models Models, Molecular Molecular Sequence Data Oxygen Phylogeny Sequence Alignment Truncated Hemoglobins
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_1553734X_v12_n1_p_Bustamante
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	todo:paper_1553734X_v12_n1_p_Bustamante
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spelling	todo:paper_1553734X_v12_n1_p_Bustamante2023-10-03T16:25:27Z Evolutionary and Functional Relationships in the Truncated Hemoglobin Family Bustamante, J.P. Radusky, L. Boechi, L. Estrin, D.A. ten Have, A. Martí, M.A. truncated hemoglobin oxygen amino acid sequence Article binding site computer model controlled study evolutionary adaptation molecular evolution molecular model oxygen affinity phylogenetic tree protein binding protein folding protein function structure activity relation biology chemistry genetics metabolism molecular evolution molecular genetics phylogeny physiology sequence alignment statistical model Amino Acid Sequence Computational Biology Evolution, Molecular Linear Models Models, Molecular Molecular Sequence Data Oxygen Phylogeny Sequence Alignment Truncated Hemoglobins Predicting function from sequence is an important goal in current biological research, and although, broad functional assignment is possible when a protein is assigned to a family, predicting functional specificity with accuracy is not straightforward. If function is provided by key structural properties and the relevant properties can be computed using the sequence as the starting point, it should in principle be possible to predict function in detail. The truncated hemoglobin family presents an interesting benchmark study due to their ubiquity, sequence diversity in the context of a conserved fold and the number of characterized members. Their functions are tightly related to O2affinity and reactivity, as determined by the association and dissociation rate constants, both of which can be predicted and analyzed using in-silico based tools. In the present work we have applied a strategy, which combines homology modeling with molecular based energy calculations, to predict and analyze function of all known truncated hemoglobins in an evolutionary context. Our results show that truncated hemoglobins present conserved family features, but that its structure is flexible enough to allow the switch from high to low affinity in a few evolutionary steps. Most proteins display moderate to high oxygen affinities and multiple ligand migration paths, which, besides some minor trends, show heterogeneous distributions throughout the phylogenetic tree, again suggesting fast functional adaptation. Our data not only deepens our comprehension of the structural basis governing ligand affinity, but they also highlight some interesting functional evolutionary trends. © 2016 Bustamante et al. Fil:Bustamante, J.P. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Boechi, L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Estrin, D.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Martí, M.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_1553734X_v12_n1_p_Bustamante
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	truncated hemoglobin oxygen amino acid sequence Article binding site computer model controlled study evolutionary adaptation molecular evolution molecular model oxygen affinity phylogenetic tree protein binding protein folding protein function structure activity relation biology chemistry genetics metabolism molecular evolution molecular genetics phylogeny physiology sequence alignment statistical model Amino Acid Sequence Computational Biology Evolution, Molecular Linear Models Models, Molecular Molecular Sequence Data Oxygen Phylogeny Sequence Alignment Truncated Hemoglobins
spellingShingle	truncated hemoglobin oxygen amino acid sequence Article binding site computer model controlled study evolutionary adaptation molecular evolution molecular model oxygen affinity phylogenetic tree protein binding protein folding protein function structure activity relation biology chemistry genetics metabolism molecular evolution molecular genetics phylogeny physiology sequence alignment statistical model Amino Acid Sequence Computational Biology Evolution, Molecular Linear Models Models, Molecular Molecular Sequence Data Oxygen Phylogeny Sequence Alignment Truncated Hemoglobins Bustamante, J.P. Radusky, L. Boechi, L. Estrin, D.A. ten Have, A. Martí, M.A. Evolutionary and Functional Relationships in the Truncated Hemoglobin Family
topic_facet	truncated hemoglobin oxygen amino acid sequence Article binding site computer model controlled study evolutionary adaptation molecular evolution molecular model oxygen affinity phylogenetic tree protein binding protein folding protein function structure activity relation biology chemistry genetics metabolism molecular evolution molecular genetics phylogeny physiology sequence alignment statistical model Amino Acid Sequence Computational Biology Evolution, Molecular Linear Models Models, Molecular Molecular Sequence Data Oxygen Phylogeny Sequence Alignment Truncated Hemoglobins
description	Predicting function from sequence is an important goal in current biological research, and although, broad functional assignment is possible when a protein is assigned to a family, predicting functional specificity with accuracy is not straightforward. If function is provided by key structural properties and the relevant properties can be computed using the sequence as the starting point, it should in principle be possible to predict function in detail. The truncated hemoglobin family presents an interesting benchmark study due to their ubiquity, sequence diversity in the context of a conserved fold and the number of characterized members. Their functions are tightly related to O2affinity and reactivity, as determined by the association and dissociation rate constants, both of which can be predicted and analyzed using in-silico based tools. In the present work we have applied a strategy, which combines homology modeling with molecular based energy calculations, to predict and analyze function of all known truncated hemoglobins in an evolutionary context. Our results show that truncated hemoglobins present conserved family features, but that its structure is flexible enough to allow the switch from high to low affinity in a few evolutionary steps. Most proteins display moderate to high oxygen affinities and multiple ligand migration paths, which, besides some minor trends, show heterogeneous distributions throughout the phylogenetic tree, again suggesting fast functional adaptation. Our data not only deepens our comprehension of the structural basis governing ligand affinity, but they also highlight some interesting functional evolutionary trends. © 2016 Bustamante et al.
format	JOUR
author	Bustamante, J.P. Radusky, L. Boechi, L. Estrin, D.A. ten Have, A. Martí, M.A.
author_facet	Bustamante, J.P. Radusky, L. Boechi, L. Estrin, D.A. ten Have, A. Martí, M.A.
author_sort	Bustamante, J.P.
title	Evolutionary and Functional Relationships in the Truncated Hemoglobin Family
title_short	Evolutionary and Functional Relationships in the Truncated Hemoglobin Family
title_full	Evolutionary and Functional Relationships in the Truncated Hemoglobin Family
title_fullStr	Evolutionary and Functional Relationships in the Truncated Hemoglobin Family
title_full_unstemmed	Evolutionary and Functional Relationships in the Truncated Hemoglobin Family
title_sort	evolutionary and functional relationships in the truncated hemoglobin family
url	http://hdl.handle.net/20.500.12110/paper_1553734X_v12_n1_p_Bustamante
work_keys_str_mv	AT bustamantejp evolutionaryandfunctionalrelationshipsinthetruncatedhemoglobinfamily AT raduskyl evolutionaryandfunctionalrelationshipsinthetruncatedhemoglobinfamily AT boechil evolutionaryandfunctionalrelationshipsinthetruncatedhemoglobinfamily AT estrinda evolutionaryandfunctionalrelationshipsinthetruncatedhemoglobinfamily AT tenhavea evolutionaryandfunctionalrelationshipsinthetruncatedhemoglobinfamily AT martima evolutionaryandfunctionalrelationshipsinthetruncatedhemoglobinfamily
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Evolutionary and Functional Relationships in the Truncated Hemoglobin Family

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