Ligand migration in methanosarcina acetivorans protoglobin: Effects of ligand binding and dimeric assembly

Protoglobin is the first globin found in Archaea. Its biological role is still unknown, although this protein can bind O2, CO, and NO reversibly in vitro. The X-ray structure of Methanosarcina acetivorans protoglobin (MaPgb) has shown that access of ligands to the heme, which is completely buried wi...

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Autores principales:	Boechi, Leonardo, Bikiel, Damian Ezequiel, Martí, Marcelo Adrián, Estrin, Dario Ariel
Publicado:	2011
Materias:	Computational chemistry Dimerization Dynamics Molecular dynamics Porphyrins Proteins Archaea Chemical process Computational technique Distinctive features Dynamical behaviors Functional mechanisms In-vitro Ligand binding Methanosarcina acetivorans Protein dimerization Protein matrix Shedding light Spatial arrangements Steric hindrances Synergistic effect X-ray structure Ligands
Acceso en línea:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_15206106_v115_n46_p13771_Forti http://hdl.handle.net/20.500.12110/paper_15206106_v115_n46_p13771_Forti
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	paper:paper_15206106_v115_n46_p13771_Forti
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spelling	paper:paper_15206106_v115_n46_p13771_Forti2023-06-08T16:19:05Z Ligand migration in methanosarcina acetivorans protoglobin: Effects of ligand binding and dimeric assembly Boechi, Leonardo Bikiel, Damian Ezequiel Martí, Marcelo Adrián Estrin, Dario Ariel Computational chemistry Dimerization Dynamics Molecular dynamics Porphyrins Proteins Archaea Chemical process Computational technique Distinctive features Dynamical behaviors Functional mechanisms In-vitro Ligand binding Methanosarcina acetivorans Protein dimerization Protein matrix Shedding light Spatial arrangements Steric hindrances Synergistic effect X-ray structure Ligands Protoglobin is the first globin found in Archaea. Its biological role is still unknown, although this protein can bind O2, CO, and NO reversibly in vitro. The X-ray structure of Methanosarcina acetivorans protoglobin (MaPgb) has shown that access of ligands to the heme, which is completely buried within the protein matrix, can be granted by two apolar tunnels, which are mainly defined by helices G and B (tunnel 1), and helices B and E (tunnel 2). Here we analyze the structural and dynamical behavior of MaPgb through molecular dynamics and computational techniques aimed at shedding light on distinctive features of ligand migration through the tunnels that may be linked to functionality. While tunnel 2 is found to be accessible to diatomic ligands in both deoxygenated and oxygenated forms of the protein, the accessibility of tunnel 1 is controlled through the synergistic effect of both the protein dimeric state and the presence of the heme-bound ligand. Thus, dimerization mainly affects the spatial arrangement of helix G, which influences the shape of tunnel 1. Ligand accessibility through this tunnel is regulated by Phe(145)G8, which can adopt open and closed conformations. Noteworthy, the ratio between open and closed states is modulated by protein dimerization and more strikingly by ligand binding. In particular, sensing of the ligand is mediated by Phe(93)E11, and the steric hindrance between Phe(93)E11 and the heme-bound ligand alters the structural and dynamical behavior of helices B and E, which facilitates opening of tunnel 1. This functional mechanism provides a basis to understand the finding that ligation favors fast rebinding from ligand binding kinetic to MaPgb. Finally, it also suggests that MaPgb might be physiologically involved in a ligand-controlled bimolecular chemical process. © 2011 American Chemical Society. Fil:Boechi, L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Bikiel, D. 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. Fil:Estrin, D. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2011 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_15206106_v115_n46_p13771_Forti http://hdl.handle.net/20.500.12110/paper_15206106_v115_n46_p13771_Forti
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	Computational chemistry Dimerization Dynamics Molecular dynamics Porphyrins Proteins Archaea Chemical process Computational technique Distinctive features Dynamical behaviors Functional mechanisms In-vitro Ligand binding Methanosarcina acetivorans Protein dimerization Protein matrix Shedding light Spatial arrangements Steric hindrances Synergistic effect X-ray structure Ligands
spellingShingle	Computational chemistry Dimerization Dynamics Molecular dynamics Porphyrins Proteins Archaea Chemical process Computational technique Distinctive features Dynamical behaviors Functional mechanisms In-vitro Ligand binding Methanosarcina acetivorans Protein dimerization Protein matrix Shedding light Spatial arrangements Steric hindrances Synergistic effect X-ray structure Ligands Boechi, Leonardo Bikiel, Damian Ezequiel Martí, Marcelo Adrián Estrin, Dario Ariel Ligand migration in methanosarcina acetivorans protoglobin: Effects of ligand binding and dimeric assembly
topic_facet	Computational chemistry Dimerization Dynamics Molecular dynamics Porphyrins Proteins Archaea Chemical process Computational technique Distinctive features Dynamical behaviors Functional mechanisms In-vitro Ligand binding Methanosarcina acetivorans Protein dimerization Protein matrix Shedding light Spatial arrangements Steric hindrances Synergistic effect X-ray structure Ligands
description	Protoglobin is the first globin found in Archaea. Its biological role is still unknown, although this protein can bind O2, CO, and NO reversibly in vitro. The X-ray structure of Methanosarcina acetivorans protoglobin (MaPgb) has shown that access of ligands to the heme, which is completely buried within the protein matrix, can be granted by two apolar tunnels, which are mainly defined by helices G and B (tunnel 1), and helices B and E (tunnel 2). Here we analyze the structural and dynamical behavior of MaPgb through molecular dynamics and computational techniques aimed at shedding light on distinctive features of ligand migration through the tunnels that may be linked to functionality. While tunnel 2 is found to be accessible to diatomic ligands in both deoxygenated and oxygenated forms of the protein, the accessibility of tunnel 1 is controlled through the synergistic effect of both the protein dimeric state and the presence of the heme-bound ligand. Thus, dimerization mainly affects the spatial arrangement of helix G, which influences the shape of tunnel 1. Ligand accessibility through this tunnel is regulated by Phe(145)G8, which can adopt open and closed conformations. Noteworthy, the ratio between open and closed states is modulated by protein dimerization and more strikingly by ligand binding. In particular, sensing of the ligand is mediated by Phe(93)E11, and the steric hindrance between Phe(93)E11 and the heme-bound ligand alters the structural and dynamical behavior of helices B and E, which facilitates opening of tunnel 1. This functional mechanism provides a basis to understand the finding that ligation favors fast rebinding from ligand binding kinetic to MaPgb. Finally, it also suggests that MaPgb might be physiologically involved in a ligand-controlled bimolecular chemical process. © 2011 American Chemical Society.
author	Boechi, Leonardo Bikiel, Damian Ezequiel Martí, Marcelo Adrián Estrin, Dario Ariel
author_facet	Boechi, Leonardo Bikiel, Damian Ezequiel Martí, Marcelo Adrián Estrin, Dario Ariel
author_sort	Boechi, Leonardo
title	Ligand migration in methanosarcina acetivorans protoglobin: Effects of ligand binding and dimeric assembly
title_short	Ligand migration in methanosarcina acetivorans protoglobin: Effects of ligand binding and dimeric assembly
title_full	Ligand migration in methanosarcina acetivorans protoglobin: Effects of ligand binding and dimeric assembly
title_fullStr	Ligand migration in methanosarcina acetivorans protoglobin: Effects of ligand binding and dimeric assembly
title_full_unstemmed	Ligand migration in methanosarcina acetivorans protoglobin: Effects of ligand binding and dimeric assembly
title_sort	ligand migration in methanosarcina acetivorans protoglobin: effects of ligand binding and dimeric assembly
publishDate	2011
url	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_15206106_v115_n46_p13771_Forti http://hdl.handle.net/20.500.12110/paper_15206106_v115_n46_p13771_Forti
work_keys_str_mv	AT boechileonardo ligandmigrationinmethanosarcinaacetivoransprotoglobineffectsofligandbindinganddimericassembly AT bikieldamianezequiel ligandmigrationinmethanosarcinaacetivoransprotoglobineffectsofligandbindinganddimericassembly AT martimarceloadrian ligandmigrationinmethanosarcinaacetivoransprotoglobineffectsofligandbindinganddimericassembly AT estrindarioariel ligandmigrationinmethanosarcinaacetivoransprotoglobineffectsofligandbindinganddimericassembly
_version_	1768542472904900608

Ligand migration in methanosarcina acetivorans protoglobin: Effects of ligand binding and dimeric assembly

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