The mechanism of nucleotide‐binding domain dimerization in the intact maltose transporter as studied by all‐atom molecular dynamics simulations

Hsu, Wei-Lin; Furuta, Tadaomi; Sakurai, Minoru

doi:10.1002/prot.25433

Cited by 7 publications

(6 citation statements)

References 46 publications

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“…These results strongly support the idea that maltose-bound MalE stimulates the ATPase activity of the transporter by promoting MalK closure [99]. This was later corroborated by the EPR work of Bordignon’s team [86] and more recently by molecular dynamic simulations [100]. Similarly, using spin-labeled MalE [45], other studies showed that ATP binding leads to the opening of MalE [68], [95].…”

Section: Step 3 and 4: Substrate Delivery And Import Mechanismsupporting

confidence: 66%

An integrated transport mechanism of the maltose ABC importer

Mächtel

Narducci

Griffith

et al. 2019

Research in Microbiology

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ATP-binding cassette (ABC) transporters use the energy of ATP hydrolysis to transport a large diversity of molecules actively across biological membranes. A combination of biochemical, biophysical, and structural studies has established the maltose transporter MalFGK2 as one of the best characterized proteins of the ABC family. MalF and MalG are the transmembrane domains, and two MalKs form a homodimer of nucleotide-binding domains. A periplasmic maltose-binding protein (MalE) delivers maltose and other maltodextrins to the transporter, and triggers its ATPase activity. Substrate import occurs in a unidirectional manner by ATP-driven conformational changes in MalK2 that allow alternating access of the substrate-binding site in MalF to each side of the membrane. In this review, we present an integrated molecular mechanism of the transport process considering all currently available information. Furthermore, we summarize remaining inconsistencies and outline possible future routes to decipher the full mechanistic details of transport by MalEFGK2 complex and that of related importer systems.

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Section: Step 3 and 4: Substrate Delivery And Import Mechanismsupporting

confidence: 66%

An integrated transport mechanism of the maltose ABC importer

Mächtel

Narducci

Griffith

et al. 2019

Research in Microbiology

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“…The analysis of the free energy landscapes for the opening-closing of the maltose transporter ATPase MaIK(2) has been conducted using enhanced-sampling molecular dynamics . In contrast, an all-atom molecular dynamics simulation dealt with the mechanism of nucleotide-binding domain dimerization in the intact Maltose Transporter …”

Section: Protein Carbohydrate Interactionsmentioning

confidence: 99%

Multifaceted Computational Modeling in Glycoscience

Pérez

Makshakova

2022

Chem. Rev.

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Glycoscience assembles all the scientific disciplines involved in studying various molecules and macromolecules containing carbohydrates and complex glycans. Such an ensemble involves one of the most extensive sets of molecules in quantity and occurrence since they occur in all microorganisms and higher organisms. Once the compositions and sequences of these molecules are established, the determination of their three-dimensional structural and dynamical features is a step toward understanding the molecular basis underlying their properties and functions. The range of the relevant computational methods capable of addressing such issues is anchored by the specificity of stereoelectronic effects from quantum chemistry to mesoscale modeling throughout molecular dynamics and mechanics and coarse-grained and docking calculations. The Review leads the reader through the detailed presentations of the applications of computational modeling. The illustrations cover carbohydrate−carbohydrate interactions, glycolipids, and N-and O-linked glycans, emphasizing their role in SARS-CoV-2. The presentation continues with the structure of polysaccharides in solution and solid-state and lipopolysaccharides in membranes. The full range of protein-carbohydrate interactions is presented, as exemplified by carbohydrate-active enzymes, transporters, lectins, antibodies, and glycosaminoglycan binding proteins. A final section features a list of 150 tools and databases to help address the many issues of structural glycobioinformatics. CONTENTS 5.1. N-and O-Linked Glycans 5.2. Structure and Dynamics of SARS-CoV-2 5.3. Structure, Function, and Dynamics of Glycolipids 6. Polysaccharides 6.1. Polysaccharides in Solution 6.2. Polysaccharides in the Solid-State 6.3. Lipolysaccharides in Membranes 7. Protein Carbohydrate Interactions 7.1. Presentation: Synopsis of the Protein Families 7.2. Insights into Glycosyltransferases 7.3. Insights into Glycosyl Hydrolases 7.4. Enzymatic Degradation of Polysaccharides in the Solid-State

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“…On the other hand, in the absence of MalE, the transmembrane helices of MalF arrange in a way that blocks the translocation pathway. MalE binding also suppresses fluctuation of the P2-loop of MalF 15 . The effect of nucleotide binding to the NBDs was also simulated, as well as its energetic and mechanistic charcterization 15 – 18 .…”

Section: Introductionmentioning

confidence: 98%

“…MalE binding also suppresses fluctuation of the P2-loop of MalF 15 . The effect of nucleotide binding to the NBDs was also simulated, as well as its energetic and mechanistic charcterization 15 – 18 . ATP binding in both pockets induces the closed form of the NBD dimer, while ATP hydrolysis triggers dimer opening 16 .…”

Section: Introductionmentioning

confidence: 98%

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

Abreu

Cruz

Oliveira

et al. 2021

Sci Rep

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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.

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The mechanism of nucleotide‐binding domain dimerization in the intact maltose transporter as studied by all‐atom molecular dynamics simulations

Cited by 7 publications

References 46 publications

An integrated transport mechanism of the maltose ABC importer

An integrated transport mechanism of the maltose ABC importer

Multifaceted Computational Modeling in Glycoscience

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

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