Cargando…
Uptake dynamics in the Lactose permease (LacY) membrane protein transporter
The sugar transporter Lactose permease (LacY) of Escherichia coli has become a prototype to understand the underlying molecular details of membrane transport. Crystal structures have trapped the protein in sugar-bound states facing the periplasm, but with narrow openings unable to accommodate sugar....
Autores principales: | , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6156506/ https://www.ncbi.nlm.nih.gov/pubmed/30254312 http://dx.doi.org/10.1038/s41598-018-32624-7 |
_version_ | 1783358118463275008 |
---|---|
author | Kimanius, D. Lindahl, E. Andersson, M. |
author_facet | Kimanius, D. Lindahl, E. Andersson, M. |
author_sort | Kimanius, D. |
collection | PubMed |
description | The sugar transporter Lactose permease (LacY) of Escherichia coli has become a prototype to understand the underlying molecular details of membrane transport. Crystal structures have trapped the protein in sugar-bound states facing the periplasm, but with narrow openings unable to accommodate sugar. Therefore, the molecular details of sugar uptake remain elusive. In this work, we have used extended simulations and metadynamics sampling to explore a putative sugar-uptake pathway and associated free energy landscape. We found an entrance at helix-pair 2 and 11, which involved lipid head groups and residues Gln 241 and Gln 359. Furthermore, the protein displayed high flexibility on the periplasmic side of Phe 27, which is located at the narrowest section of the pathway. Interactions to Phe 27 enabled passage into the binding site, which was associated with a 24 ± 4 kJ/mol binding free energy in excellent agreement with an independent binding free energy calculation and experimental data. Two free energy minima corresponding to the two possible binding poses of the lactose analog β-D-galactopyranosyl-1-thio-β-D-galactopyranoside (TDG) were aligned with the crystal structure-binding pocket. This work outlines the chemical environment of a putative periplasmic sugar pathway and paves way for understanding substrate affinity and specificity in LacY. |
format | Online Article Text |
id | pubmed-6156506 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-61565062018-09-28 Uptake dynamics in the Lactose permease (LacY) membrane protein transporter Kimanius, D. Lindahl, E. Andersson, M. Sci Rep Article The sugar transporter Lactose permease (LacY) of Escherichia coli has become a prototype to understand the underlying molecular details of membrane transport. Crystal structures have trapped the protein in sugar-bound states facing the periplasm, but with narrow openings unable to accommodate sugar. Therefore, the molecular details of sugar uptake remain elusive. In this work, we have used extended simulations and metadynamics sampling to explore a putative sugar-uptake pathway and associated free energy landscape. We found an entrance at helix-pair 2 and 11, which involved lipid head groups and residues Gln 241 and Gln 359. Furthermore, the protein displayed high flexibility on the periplasmic side of Phe 27, which is located at the narrowest section of the pathway. Interactions to Phe 27 enabled passage into the binding site, which was associated with a 24 ± 4 kJ/mol binding free energy in excellent agreement with an independent binding free energy calculation and experimental data. Two free energy minima corresponding to the two possible binding poses of the lactose analog β-D-galactopyranosyl-1-thio-β-D-galactopyranoside (TDG) were aligned with the crystal structure-binding pocket. This work outlines the chemical environment of a putative periplasmic sugar pathway and paves way for understanding substrate affinity and specificity in LacY. Nature Publishing Group UK 2018-09-25 /pmc/articles/PMC6156506/ /pubmed/30254312 http://dx.doi.org/10.1038/s41598-018-32624-7 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Kimanius, D. Lindahl, E. Andersson, M. Uptake dynamics in the Lactose permease (LacY) membrane protein transporter |
title | Uptake dynamics in the Lactose permease (LacY) membrane protein transporter |
title_full | Uptake dynamics in the Lactose permease (LacY) membrane protein transporter |
title_fullStr | Uptake dynamics in the Lactose permease (LacY) membrane protein transporter |
title_full_unstemmed | Uptake dynamics in the Lactose permease (LacY) membrane protein transporter |
title_short | Uptake dynamics in the Lactose permease (LacY) membrane protein transporter |
title_sort | uptake dynamics in the lactose permease (lacy) membrane protein transporter |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6156506/ https://www.ncbi.nlm.nih.gov/pubmed/30254312 http://dx.doi.org/10.1038/s41598-018-32624-7 |
work_keys_str_mv | AT kimaniusd uptakedynamicsinthelactosepermeaselacymembraneproteintransporter AT lindahle uptakedynamicsinthelactosepermeaselacymembraneproteintransporter AT anderssonm uptakedynamicsinthelactosepermeaselacymembraneproteintransporter |