期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 116, 期 25, 页码 12275-12284出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1904210116
关键词
multidrug resistance; membrane protein structure; MATE transporter; inward-facing; conformation; lipids
资金
- Max Planck Society
- Deutsche Forschungsgemeinschaft (Cluster of Excellence Macromolecular Complexes Frankfurt)
- Transport and Communication across Biological Membranes [CRC807]
- Austrian Ministry for Education, Science and Research (JPI-HDHL Project) [BMWFW-10.420/0005-W/V/3c/2017]
- Austrian Ministry for Education, Science and Research (HSRSM Grant Omics Center Graz, BioTechMed-Graz)
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.
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