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

ATP binding cassette (ABC) transporters employ ATP hydrolysis to harness substrate translocation across membranes. The Escherichia coli MalFGK 2 E maltose importer is an example of a type I ABC importer and a model system for this class of ABC transporters. The MalFGK 2 E importer is responsible for...

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Bibliographic Details
Published in:Scientific reports 2021-05, Vol.11 (1), p.10591-10591, Article 10591
Main Authors: Abreu, Bárbara, Cruz, Carlos, Oliveira, A. Sofia F., Soares, Cláudio M.
Format: Article
Language:English
Subjects:
631/45
631/45/535
631/45/535/1267
631/45/612
631/45/612/1237
631/57
631/57/2266
ABC transporters
ATP
Cytoplasm
E coli
Humanities and Social Sciences
Hydrolysis
Maltose
multidisciplinary
Proteins
Science
Science (multidisciplinary)
Simulation
Spheres
Translocation
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Summary:ATP binding cassette (ABC) transporters employ ATP hydrolysis to harness substrate translocation across membranes. The Escherichia coli MalFGK 2 E maltose importer is an example of a type I ABC importer and a model system for this class of ABC transporters. The MalFGK 2 E 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.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-021-89556-y