Zakrzewska, Sandra and Mehdipour, Ahmad Reza and Malviya, Viveka Nand and Nonaka, Tsuyoshi and Koepke, Juergen and Muenke, Cornelia and Hausner, Winfried and Hummer, Gerhard and Safarian, Schara and Michel, Hartmut (2019) Inward-facing conformation of a multidrug resistance MATE family transporter. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 116 (25). pp. 12275-12284. ISSN 0027-8424,
Full text not available from this repository. (Request a copy)Abstract
Multidrug and toxic compound extrusion (MATE) transporters mediate excretion of xenobiotics and toxic metabolites, thereby conferring multidrug resistance in bacterial pathogens and cancer cells. Structural information on the alternate conformational states and knowledge of the detailed mechanism of MATE transport are of great importance for drug development. However, the structures of MATE transporters are only known in V-shaped outward-facing conformations. Here, we present the crystal structure of a MATE transporter from Pyrococcus furiosus (PfMATE) in the long-soughtafter inward-facing state, which was obtained after crystallization in the presence of native lipids. Transition from the outward-facing state to the inward-facing state involves rigid body movements of transmembrane helices (TMs) 2-6 and 8-12 to form an inverted V, facilitated by a loose binding of TM1 and TM7 to their respective bundles and their conformational flexibility. The inward-facing structure of PfMATE in combination with the outward-facing one supports an alternating access mechanism for the MATE family transporters.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | MACROMOLECULAR STRUCTURES; MOLECULAR REPLACEMENT; MEMBRANE-PROTEINS; PHASE INFORMATION; CRYSTAL-STRUCTURE; OMIT MAPS; EXTRUSION; REFINEMENT; DYNAMICS; NORM; multidrug resistance; membrane protein structure; MATE transporter; inward-facing; conformation; lipids |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie > Lehrstuhl für Mikrobiologie (Archaeenzentrum) > Prof. Dr. Dina Grohmann |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 08 Apr 2020 06:49 |
| Last Modified: | 08 Apr 2020 06:49 |
| URI: | https://pred.uni-regensburg.de/id/eprint/26824 |
Actions (login required)
 |
View Item |
