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ATP Hydrolysis Induced Conformational Changes in the Vitamin B(12) Transporter BtuCD Revealed by MD Simulations

ATP binding cassette (ABC) transporters utilize the energy of ATP hydrolysis to uni-directionally transport substrates across cell membrane. ATP hydrolysis occurs at the nucleotide-binding domain (NBD) dimer interface of ABC transporters, whereas substrate translocation takes place at the translocat...

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Autores principales: Pan, Chao, Weng, Jingwei, Wang, Wenning
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5117765/
https://www.ncbi.nlm.nih.gov/pubmed/27870912
http://dx.doi.org/10.1371/journal.pone.0166980
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author Pan, Chao
Weng, Jingwei
Wang, Wenning
author_facet Pan, Chao
Weng, Jingwei
Wang, Wenning
author_sort Pan, Chao
collection PubMed
description ATP binding cassette (ABC) transporters utilize the energy of ATP hydrolysis to uni-directionally transport substrates across cell membrane. ATP hydrolysis occurs at the nucleotide-binding domain (NBD) dimer interface of ABC transporters, whereas substrate translocation takes place at the translocation pathway between the transmembrane domains (TMDs), which is more than 30 angstroms away from the NBD dimer interface. This raises the question of how the hydrolysis energy released at NBDs is “transmitted” to trigger the conformational changes at TMDs. Using molecular dynamics (MD) simulations, we studied the post-hydrolysis state of the vitamin B(12) importer BtuCD. Totally 3-μs MD trajectories demonstrate a predominantly asymmetric arrangement of the NBD dimer interface, with the ADP-bound site disrupted and the ATP-bound site preserved in most of the trajectories. TMDs response to ATP hydrolysis by separation of the L-loops and opening of the cytoplasmic gate II, indicating that hydrolysis of one ATP could facilitate substrate translocation by opening the cytoplasmic end of translocation pathway. It was also found that motions of the L-loops and the cytoplasmic gate II are coupled with each other through a contiguous interaction network involving a conserved Asn83 on the extended stretch preceding TM3 helix plus the cytoplasmic end of TM2/6/7 helix bundle. These findings entail a TMD-NBD communication mechanism for type II ABC importers.
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spelling pubmed-51177652016-12-15 ATP Hydrolysis Induced Conformational Changes in the Vitamin B(12) Transporter BtuCD Revealed by MD Simulations Pan, Chao Weng, Jingwei Wang, Wenning PLoS One Research Article ATP binding cassette (ABC) transporters utilize the energy of ATP hydrolysis to uni-directionally transport substrates across cell membrane. ATP hydrolysis occurs at the nucleotide-binding domain (NBD) dimer interface of ABC transporters, whereas substrate translocation takes place at the translocation pathway between the transmembrane domains (TMDs), which is more than 30 angstroms away from the NBD dimer interface. This raises the question of how the hydrolysis energy released at NBDs is “transmitted” to trigger the conformational changes at TMDs. Using molecular dynamics (MD) simulations, we studied the post-hydrolysis state of the vitamin B(12) importer BtuCD. Totally 3-μs MD trajectories demonstrate a predominantly asymmetric arrangement of the NBD dimer interface, with the ADP-bound site disrupted and the ATP-bound site preserved in most of the trajectories. TMDs response to ATP hydrolysis by separation of the L-loops and opening of the cytoplasmic gate II, indicating that hydrolysis of one ATP could facilitate substrate translocation by opening the cytoplasmic end of translocation pathway. It was also found that motions of the L-loops and the cytoplasmic gate II are coupled with each other through a contiguous interaction network involving a conserved Asn83 on the extended stretch preceding TM3 helix plus the cytoplasmic end of TM2/6/7 helix bundle. These findings entail a TMD-NBD communication mechanism for type II ABC importers. Public Library of Science 2016-11-21 /pmc/articles/PMC5117765/ /pubmed/27870912 http://dx.doi.org/10.1371/journal.pone.0166980 Text en © 2016 Pan et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Pan, Chao
Weng, Jingwei
Wang, Wenning
ATP Hydrolysis Induced Conformational Changes in the Vitamin B(12) Transporter BtuCD Revealed by MD Simulations
title ATP Hydrolysis Induced Conformational Changes in the Vitamin B(12) Transporter BtuCD Revealed by MD Simulations
title_full ATP Hydrolysis Induced Conformational Changes in the Vitamin B(12) Transporter BtuCD Revealed by MD Simulations
title_fullStr ATP Hydrolysis Induced Conformational Changes in the Vitamin B(12) Transporter BtuCD Revealed by MD Simulations
title_full_unstemmed ATP Hydrolysis Induced Conformational Changes in the Vitamin B(12) Transporter BtuCD Revealed by MD Simulations
title_short ATP Hydrolysis Induced Conformational Changes in the Vitamin B(12) Transporter BtuCD Revealed by MD Simulations
title_sort atp hydrolysis induced conformational changes in the vitamin b(12) transporter btucd revealed by md simulations
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5117765/
https://www.ncbi.nlm.nih.gov/pubmed/27870912
http://dx.doi.org/10.1371/journal.pone.0166980
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