Journal
NATURE COMMUNICATIONS
Volume 9, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-017-02493-1
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Funding
- CREST
- Center of Innovation Program (COI) from the Japan Science and Technology Agency (JST)
- Program for the Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation
- Network Joint Research Center for Materials and Devices
- Dynamic Alliance for Open Innovation Bridging Human, Environment and Materials from the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT)
- Japan Society for the Promotion of Science (JSPS) [17H03983]
- Japan Agency for Medical Research and Development (AMED)
- Grants-in-Aid for Scientific Research [16K15518, 17H03983] Funding Source: KAKEN
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AcrB is the major multidrug exporter in Escherichia coli. Although several substrate-entrances have been identified, the specificity of these various transport paths remains unclear. Here we present evidence for a substrate channel (channel 3) from the central cavity of the AcrB trimer, which is connected directly to the deep pocket without first passing the switch-loop and the proximal pocket. Planar aromatic cations, such as ethidium, prefer channel 3 to channels 1 and 2. The efflux through channel 3 increases by targeted mutations and is not in competition with the export of drugs such as minocycline and erythromycin through channels 1 and 2. A switch-loop mutant, in which the pathway from the proximal to the deep pocket is hindered, can export only channel 3-utilizing drugs. The usage of multiple entrances thus contributes to the recognition and transport of a wide range of drugs with different physicochemical properties.
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