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

Bosshart, Patrick D.; Kalbermatter, David; Bonetti, Sara; Fotiadis, Dimitrios (2019). Mechanistic basis of L-lactate transport in the SLC16 solute carrier family. Nature communications, 10(1), p. 2649. Nature Publishing Group 10.1038/s41467-019-10566-6

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Biochemistry and Molecular Medicine

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Bosshart, Patrick; Kalbermatter, David; Bonetti, Sara and Fotiadis, Dimitrios José

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

2041-1723

Publisher:

Nature Publishing Group

Funders:

[4] Swiss National Science Foundation
[65] NCCR TransCure

Language:

English

Submitter:

Sara Bonetti

Date Deposited:

27 Aug 2019 12:51

Last Modified:

01 Sep 2019 02:39

Publisher DOI:

10.1038/s41467-019-10566-6

PubMed ID:

31201333

BORIS DOI:

10.7892/boris.132563

URI:

https://boris.unibe.ch/id/eprint/132563

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