Multidrug and toxin extrusion (MATE; SLC47A) proteins are membrane transporters mediating the excretion of organic cations and zwitterions into bile and urine and thereby contributing to the hepatic and renal elimination of many xenobiotics. This family has two members: MATE-1 and MATE-2. MATE-1 is an H+/organic cation antiporter and is a human orthologue of the bacterial NorM. Human MATE-2 is a homolog of human MATE-1 and it has two splice variants, MATE-K and MATE-B, among which the former is the active form of the SLC47A2 gene.
Human MATE-1 is highly expressed in a wide range of tissues and organs, including the kidney, liver, skeletal, muscle, and several other tissues. In contrast, MATE2-K exhibits a kidney-specific expression. Both are localized in the brush-border membrane of proximal tubules. In the kidney and liver, MATEs work in concert with organic cation transporters (OCTs), together representing an eliminatory pathway for organic cations in humans. MATE-1 also acts as an efflux transporter in other tissues.
Recent advances in the study of the substrate specificity, protein structure, gene polymorphisms, tissue expression, and clinical studies have demonstrated that MATEs play an important role in the pharmacokinetics, pharmacodynamics/toxicodynamics and pharmacogenomics of cationic drugs. Moreover, clinical studies have investigated the impact of MATEs on the inter-individual variability of cationic drugs, which helps to establish personalized pharmacotherapy. Moreover, the potential role of MATE proteins in renal drug-drug interaction is of increasing interest.
Here, we give an introduction of these two human MATE transporters focusing on the current knowledge on their structural and molecular features, expression and localization in different tissues, important aspects on regulation, and their functional role in drug transport.
For a detailed analysis of membrane protein structures and interactions, as well as for wider use and future applications, membrane proteins are required to be isolated from the naïve membrane environment and then adapted to different membrane-like environments that preserve the protein functional activity. This can be technically difficult. To obtain MATEs in their functional formats, Creative Biolabs here presents our versatile Magic™ membrane protein production platform, which offers various reconstitution systems that are effective in solubilizing and stabilizing your protein of interest, to help advance your brilliant studies. Available functional formats include detergent micelles, proteoliposomes, nanodiscs, lipoparticles, and polymers.
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