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...

Descripción completa

Detalles Bibliográficos
Autores principales: Forti, F., Boechi, L., Bikiel, D., Martí, M.A., Nardini, M., Bolognesi, M., Viappiani, C., Estrin, D., Luque, F.J.
Formato: JOUR
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: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 todo:paper_15206106_v115_n46_p13771_Forti
record_format dspace
spelling todo:paper_15206106_v115_n46_p13771_Forti2023-10-03T16:20:23Z Ligand migration in methanosarcina acetivorans protoglobin: Effects of ligand binding and dimeric assembly Forti, F. Boechi, L. Bikiel, D. Martí, M.A. Nardini, M. Bolognesi, M. Viappiani, C. Estrin, D. Luque, F.J. 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. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar 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
Forti, F.
Boechi, L.
Bikiel, D.
Martí, M.A.
Nardini, M.
Bolognesi, M.
Viappiani, C.
Estrin, D.
Luque, F.J.
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.
format JOUR
author Forti, F.
Boechi, L.
Bikiel, D.
Martí, M.A.
Nardini, M.
Bolognesi, M.
Viappiani, C.
Estrin, D.
Luque, F.J.
author_facet Forti, F.
Boechi, L.
Bikiel, D.
Martí, M.A.
Nardini, M.
Bolognesi, M.
Viappiani, C.
Estrin, D.
Luque, F.J.
author_sort Forti, F.
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
url http://hdl.handle.net/20.500.12110/paper_15206106_v115_n46_p13771_Forti
work_keys_str_mv AT fortif ligandmigrationinmethanosarcinaacetivoransprotoglobineffectsofligandbindinganddimericassembly
AT boechil ligandmigrationinmethanosarcinaacetivoransprotoglobineffectsofligandbindinganddimericassembly
AT bikield ligandmigrationinmethanosarcinaacetivoransprotoglobineffectsofligandbindinganddimericassembly
AT martima ligandmigrationinmethanosarcinaacetivoransprotoglobineffectsofligandbindinganddimericassembly
AT nardinim ligandmigrationinmethanosarcinaacetivoransprotoglobineffectsofligandbindinganddimericassembly
AT bolognesim ligandmigrationinmethanosarcinaacetivoransprotoglobineffectsofligandbindinganddimericassembly
AT viappianic ligandmigrationinmethanosarcinaacetivoransprotoglobineffectsofligandbindinganddimericassembly
AT estrind ligandmigrationinmethanosarcinaacetivoransprotoglobineffectsofligandbindinganddimericassembly
AT luquefj ligandmigrationinmethanosarcinaacetivoransprotoglobineffectsofligandbindinganddimericassembly
_version_ 1807320343418765312

Ejemplares similares