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Inward-facing conformation of a multidrug resistance MATE family transporter

June 2019. A team of Frankfurt scientists are the first to trap an important type of multidrug transport protein in its inward facing conformation. Their results provide an alternative view on the  mode of action for the MATE family of multidrug transporters.

Multidrug and toxic compound extrusion (MATE) transporter proteins mediate excretion of xenobiotics and toxic metabolites, thereby conferring multidrug resistance in bacterial pathogens and cancer cells. Structural information on the alternate conformational states of the transporter proteins and knowledge of the detailed mechanism of MATE transport are of great importance for drug development.

Crystal structures of representative members of the three MATE subfamilies have been published but since all of these structures represent only an outward-facing state, a detailed understanding of the complete transport cycle remained elusive.

A team of scientists at the Max Planck Institute of Biophysics in Frankfurt,  led by Hartmut Michel, succeeded by using native lipids. Their approach allowed trapping and visualization of the MATE transporter from the bacterium Pyrococcus furiosus in an inward-facing conformation. 

Based on their new data, the team could establish a framework of the structural changes that occur during the transition between the inward- and outward-facing conformations of the MATE transporter.

Their work highlights the importance of native lipids and provides an alternative view on the function and mechanism of action for the MATE family transporters.

MATE transporters occur in a wide range of organisms and are present in all domains of life. As secondary active transporters, they utilize transmembrane electrochemical ion gradients (Na+ or H+) to drive the export of xenobiotics or cytotoxic metabolic waste products with specificity mainly for organic cations.

MATE transporters confer resistance, for example, to fluoroquinolones, aminoglycoside antibiotics, and anticancer chemotherapeutical agents, thus serving as promising drug targets in the fight against multidrug resistance.


Hartmut Michel, Department of Molecular Membrane Biology, Max Planck Institute of Biophysics, Frankfurt/Main, Germany, Hartmut.Miche(at)biophys.mpg.de


Sandra Zakrzewska, Ahmad Reza Mehdipour, Viveka Nand Malviya, Tsuyoshi Nonaka, Juergen Koepke, Cornelia Muenke, Winfried Hausner, Gerhard Hummer, Schara Safarian and Hartmut Michel (2019) Inward-facing conformation of a multidrug resistance MATE family transporter. Proceedings of the National Academy of Sciences of the USA 116: 12275-12284, first published online 3 June 2019. http://dx.doi.org/10.1073/pnas.1904210116