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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Bacterial Proteins / chemistry*
-
Bacterial Proteins / isolation & purification
-
Bacterial Proteins / metabolism
-
Cell Membrane / metabolism
-
Crystallography, X-Ray
-
Ion Transport / physiology
-
Lactic Acid / metabolism*
-
Ligands
-
Monocarboxylic Acid Transporters / chemistry*
-
Monocarboxylic Acid Transporters / isolation & purification
-
Monocarboxylic Acid Transporters / metabolism
-
Muscle Proteins / chemistry
-
Protein Binding / physiology
-
Protein Structure, Tertiary
-
Recombinant Proteins / chemistry
-
Recombinant Proteins / isolation & purification
-
Recombinant Proteins / metabolism
-
Sequence Alignment
-
Sequence Homology, Amino Acid
-
Structure-Activity Relationship
-
Symporters / chemistry
Substances
-
Bacterial Proteins
-
Ligands
-
Monocarboxylic Acid Transporters
-
Muscle Proteins
-
Recombinant Proteins
-
SLC16A4 protein, human
-
Symporters
-
monocarboxylate transport protein 1
-
Lactic Acid