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


ABSTRACT: 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.

SUBMITTER: Bosshart PD 

PROVIDER: S-EPMC6573034 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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

Bosshart Patrick D PD   Kalbermatter David D   Bonetti Sara S   Fotiadis Dimitrios D  

Nature communications 20190614 1


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 conformatio  ...[more]

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