Crystal structures of multidrug efflux transporters from Burkholderia pseudomallei suggest details of transport mechanism

Kato, Takaaki; Okada, Ui; Hung, Li-Wei; Yamashita, Eiki; Kim, Huengbok; Kim, Chang Yub; Terwilliger, Thomas Charles; Schweizer, Herbert P; Murakami, Satoshi

doi:10.1073/pnas.2215072120

Title: Crystal structures of multidrug efflux transporters from Burkholderia pseudomallei suggest details of transport mechanism

Journal Article · Tue Jul 18 00:00:00 UTC 2023 · Proceedings of the National Academy of Sciences of the United States of America

DOI: https://doi.org/10.1073/pnas.2215072120 · OSTI ID:2426771

Kato, Takaaki ^[1]; Okada, Ui ^[1];

^[2]; Yamashita, Eiki ^[3]; Kim, Huengbok ^[2];

^[2];

^[4]; Schweizer, Herbert P ^[5]; Murakami, Satoshi ^[1]

Tokyo Institute of Technology (Japan)
Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
Osaka Univ. (Japan)
Los Alamos National Laboratory (LANL), Los Alamos, NM (United States); New Mexico Consortium, Los Alamos, NM (United States)
Northern Arizona Univ., Flagstaff, AZ (United States)

BpeB and BpeF are multidrug efflux transporters from Burkholderia pseudomallei that enable multidrug resistance. Here, we report the crystal structures of BpeB and BpeF at 2.94 Å and 3.0 Å resolution, respectively. BpeB was found as an asymmetric trimer, consistent with the widely-accepted functional rotation mechanism for this type of transporter. One of the monomers has a distinct structure that we interpret as an intermediate along this functional cycle. Additionally, a detergent molecule bound in a previously undescribed binding site provides insights into substrate translocation through the pathway. BpeF shares structural similarities with the crystal structure of OqxB from Klebsiella pneumoniae, where both are symmetric trimers composed of three “binding”-state monomers. The structures of BpeB and BpeF further our understanding of the functional mechanisms of transporters belonging to the HAE1-RND superfamily.

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Research Organization:: Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)

Sponsoring Organization:: JSPS KAKENHI; National Institutes of Health (NIH); USDOE

Grant/Contract Number:: 89233218CNA000001

OSTI ID:: 2426771

Report Number(s):: LA-UR--22-28088

Journal Information:: Proceedings of the National Academy of Sciences of the United States of America, Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Issue: 29 Vol. 120; ISSN 0027-8424

Publisher:: National Academy of SciencesCopyright Statement

Country of Publication:: United States

Language:: English

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59 BASIC BIOLOGICAL SCIENCES
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Title: Crystal structures of multidrug efflux transporters from Burkholderia pseudomallei suggest details of transport mechanism

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