Mechanistic basis of L-lactate transport in the SLC16 solute carrier family

In human and other mammalian cells, transport of L-lactate across plasma membranes is mainly catalyzed by monocarboxylate transporters (MCTs) of the SLC16 solute carrier family. MCTs play an important role in cancer metabolism and are promising targets for tumor treatment. Here, we report the crysta...

Descripción completa

Detalles Bibliográficos
Autores principales: Bosshart, Patrick D., Kalbermatter, David, Bonetti, Sara, Fotiadis, Dimitrios
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6573034/
https://www.ncbi.nlm.nih.gov/pubmed/31201333
http://dx.doi.org/10.1038/s41467-019-10566-6
_version_ 1783427769536872448
author Bosshart, Patrick D.
Kalbermatter, David
Bonetti, Sara
Fotiadis, Dimitrios
author_facet Bosshart, Patrick D.
Kalbermatter, David
Bonetti, Sara
Fotiadis, Dimitrios
author_sort Bosshart, Patrick D.
collection PubMed
description In human and other mammalian cells, transport of L-lactate across plasma membranes is mainly catalyzed by monocarboxylate transporters (MCTs) of the SLC16 solute carrier family. MCTs play an important role in cancer metabolism and are promising targets for tumor treatment. Here, we report the crystal structures of an SLC16 family homologue with two different bound ligands at 2.54 and 2.69 Å resolution. The structures show the transporter in the pharmacologically relevant outward-open conformation. Structural information together with a detailed structure-based analysis of the transport function provide important insights into the molecular working mechanisms of ligand binding and L-lactate transport.
format Online
Article
Text
id pubmed-6573034
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-65730342019-06-24 Mechanistic basis of L-lactate transport in the SLC16 solute carrier family Bosshart, Patrick D. Kalbermatter, David Bonetti, Sara Fotiadis, Dimitrios Nat Commun Article In human and other mammalian cells, transport of L-lactate across plasma membranes is mainly catalyzed by monocarboxylate transporters (MCTs) of the SLC16 solute carrier family. MCTs play an important role in cancer metabolism and are promising targets for tumor treatment. Here, we report the crystal structures of an SLC16 family homologue with two different bound ligands at 2.54 and 2.69 Å resolution. The structures show the transporter in the pharmacologically relevant outward-open conformation. Structural information together with a detailed structure-based analysis of the transport function provide important insights into the molecular working mechanisms of ligand binding and L-lactate transport. Nature Publishing Group UK 2019-06-14 /pmc/articles/PMC6573034/ /pubmed/31201333 http://dx.doi.org/10.1038/s41467-019-10566-6 Text en © The Author(s) 2019 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
Bosshart, Patrick D.
Kalbermatter, David
Bonetti, Sara
Fotiadis, Dimitrios
Mechanistic basis of L-lactate transport in the SLC16 solute carrier family
title Mechanistic basis of L-lactate transport in the SLC16 solute carrier family
title_full Mechanistic basis of L-lactate transport in the SLC16 solute carrier family
title_fullStr Mechanistic basis of L-lactate transport in the SLC16 solute carrier family
title_full_unstemmed Mechanistic basis of L-lactate transport in the SLC16 solute carrier family
title_short Mechanistic basis of L-lactate transport in the SLC16 solute carrier family
title_sort mechanistic basis of l-lactate transport in the slc16 solute carrier family
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6573034/
https://www.ncbi.nlm.nih.gov/pubmed/31201333
http://dx.doi.org/10.1038/s41467-019-10566-6
work_keys_str_mv AT bosshartpatrickd mechanisticbasisofllactatetransportintheslc16solutecarrierfamily
AT kalbermatterdavid mechanisticbasisofllactatetransportintheslc16solutecarrierfamily
AT bonettisara mechanisticbasisofllactatetransportintheslc16solutecarrierfamily
AT fotiadisdimitrios mechanisticbasisofllactatetransportintheslc16solutecarrierfamily

Ejemplares similares