ATP hydrolysis and nucleotide exit enhance maltose translocation in the MalFGK2E importer

Abstract ATP binding cassette (ABC) transporters employ ATP hydrolysis to harness substrate translocation across membranes. The Escherichia coli MalFGK2E maltose importer is an example of a type I ABC importer and a model system for this class of ABC transporters. The MalFGK2E importer is responsibl...

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Autores principales:	Bárbara Abreu, Carlos Cruz, A. Sofia F. Oliveira, Cláudio M. Soares
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4903ba4df38e4237b2705ccb0279e2a6
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spelling	oai:doaj.org-article:4903ba4df38e4237b2705ccb0279e2a62021-12-02T15:45:21ZATP hydrolysis and nucleotide exit enhance maltose translocation in the MalFGK2E importer10.1038/s41598-021-89556-y2045-2322https://doaj.org/article/4903ba4df38e4237b2705ccb0279e2a62021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-89556-yhttps://doaj.org/toc/2045-2322Abstract ATP binding cassette (ABC) transporters employ ATP hydrolysis to harness substrate translocation across membranes. The Escherichia coli MalFGK2E maltose importer is an example of a type I ABC importer and a model system for this class of ABC transporters. The MalFGK2E importer is responsible for the intake of malto-oligossacharides in E.coli. Despite being extensively studied, little is known about the effect of ATP hydrolysis and nucleotide exit on substrate transport. In this work, we studied this phenomenon using extensive molecular dynamics simulations (MD) along with potential of mean force calculations of maltose transport across the pore, in the pre-hydrolysis, post-hydrolysis and nucleotide-free states. We concluded that ATP hydrolysis and nucleotide exit trigger conformational changes that result in the decrease of energetic barriers to maltose translocation towards the cytoplasm, with a concomitant increase of the energy barrier in the periplasmic side of the pore, contributing for the irreversibility of the process. We also identified key residues that aid in positioning and orientation of maltose, as well as a novel binding pocket for maltose in MalG. Additionally, ATP hydrolysis leads to conformations similar to the nucleotide-free state. This study shows the contribution of ATP hydrolysis and nucleotide exit in the transport cycle, shedding light on ABC type I importer mechanisms.Bárbara AbreuCarlos CruzA. Sofia F. OliveiraCláudio M. SoaresNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-17 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Bárbara Abreu Carlos Cruz A. Sofia F. Oliveira Cláudio M. Soares ATP hydrolysis and nucleotide exit enhance maltose translocation in the MalFGK2E importer
description	Abstract ATP binding cassette (ABC) transporters employ ATP hydrolysis to harness substrate translocation across membranes. The Escherichia coli MalFGK2E maltose importer is an example of a type I ABC importer and a model system for this class of ABC transporters. The MalFGK2E importer is responsible for the intake of malto-oligossacharides in E.coli. Despite being extensively studied, little is known about the effect of ATP hydrolysis and nucleotide exit on substrate transport. In this work, we studied this phenomenon using extensive molecular dynamics simulations (MD) along with potential of mean force calculations of maltose transport across the pore, in the pre-hydrolysis, post-hydrolysis and nucleotide-free states. We concluded that ATP hydrolysis and nucleotide exit trigger conformational changes that result in the decrease of energetic barriers to maltose translocation towards the cytoplasm, with a concomitant increase of the energy barrier in the periplasmic side of the pore, contributing for the irreversibility of the process. We also identified key residues that aid in positioning and orientation of maltose, as well as a novel binding pocket for maltose in MalG. Additionally, ATP hydrolysis leads to conformations similar to the nucleotide-free state. This study shows the contribution of ATP hydrolysis and nucleotide exit in the transport cycle, shedding light on ABC type I importer mechanisms.
format	article
author	Bárbara Abreu Carlos Cruz A. Sofia F. Oliveira Cláudio M. Soares
author_facet	Bárbara Abreu Carlos Cruz A. Sofia F. Oliveira Cláudio M. Soares
author_sort	Bárbara Abreu
title	ATP hydrolysis and nucleotide exit enhance maltose translocation in the MalFGK2E importer
title_short	ATP hydrolysis and nucleotide exit enhance maltose translocation in the MalFGK2E importer
title_full	ATP hydrolysis and nucleotide exit enhance maltose translocation in the MalFGK2E importer
title_fullStr	ATP hydrolysis and nucleotide exit enhance maltose translocation in the MalFGK2E importer
title_full_unstemmed	ATP hydrolysis and nucleotide exit enhance maltose translocation in the MalFGK2E importer
title_sort	atp hydrolysis and nucleotide exit enhance maltose translocation in the malfgk2e importer
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/4903ba4df38e4237b2705ccb0279e2a6
work_keys_str_mv	AT barbaraabreu atphydrolysisandnucleotideexitenhancemaltosetranslocationinthemalfgk2eimporter AT carloscruz atphydrolysisandnucleotideexitenhancemaltosetranslocationinthemalfgk2eimporter AT asofiafoliveira atphydrolysisandnucleotideexitenhancemaltosetranslocationinthemalfgk2eimporter AT claudiomsoares atphydrolysisandnucleotideexitenhancemaltosetranslocationinthemalfgk2eimporter
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ATP hydrolysis and nucleotide exit enhance maltose translocation in the MalFGK2E importer

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