Structural insights into trehalose capture and translocation by mycobacterial LpqY-SugABC

Jingxi Liang; Xiuna Yang; Tianyu Hu; Yan Gao; Qi Yang; Haitao Yang; Wei Peng; Xiaoting Zhou; Luke W Guddat; Bing Zhang; Zihe Rao; Fengjiang Liu

doi:10.1016/j.str.2023.07.014

Structural insights into trehalose capture and translocation by mycobacterial LpqY-SugABC

Structure. 2023 Oct 5;31(10):1158-1165.e3. doi: 10.1016/j.str.2023.07.014. Epub 2023 Aug 23.

Authors

Jingxi Liang¹, Xiuna Yang², Tianyu Hu², Yan Gao², Qi Yang³, Haitao Yang², Wei Peng³, Xiaoting Zhou⁴, Luke W Guddat⁵, Bing Zhang⁶, Zihe Rao⁷, Fengjiang Liu⁸

Affiliations

¹ State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, China; Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai, China; Innovative Center for Pathogen Research, Guangzhou Laboratory, Guangzhou, China.
² Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
³ Innovative Center for Pathogen Research, Guangzhou Laboratory, Guangzhou, China.
⁴ The State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, School of Life Sciences, Inner Mongolia University, Hohhot, China.
⁵ School of Chemistry and Molecular Biosciences, the University of Queensland, Brisbane, QLD, Australia.
⁶ Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai, China. Electronic address: zhangbing@shanghaitech.edu.cn.
⁷ State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, China; Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai, China; Innovative Center for Pathogen Research, Guangzhou Laboratory, Guangzhou, China; National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, CAS, Beijing, China; Laboratory of Structural Biology, Tsinghua University, Beijing, China. Electronic address: raozh@tsinghua.edu.cn.
⁸ Innovative Center for Pathogen Research, Guangzhou Laboratory, Guangzhou, China. Electronic address: liu_fengjiang@gzlab.ac.cn.

PMID: 37619560
DOI: 10.1016/j.str.2023.07.014

Abstract

The human pathogen, Mycobacterium tuberculosis (Mtb) relies heavily on trehalose for both survival and pathogenicity. The type I ATP-binding cassette (ABC) transporter LpqY-SugABC is the only trehalose import pathway in Mtb. Conformational dynamics of ABC transporters is an important feature to explain how they operate, but experimental structures are determined in a static environment. Therefore, a detailed transport mechanism cannot be elucidated because there is a lack of intermediate structures. Here, we used single-particle cryo-electron microscopy (cryo-EM) to determine the structure of the Mycobacterium smegmatis (M. smegmatis) trehalose-specific importer LpqY-SugABC complex in five different conformations. These structures have been classified and reconstructed from a single cryo-EM dataset. This study allows a comprehensive understanding of the trehalose recycling mechanism in Mycobacteria and also demonstrates the potential of single-particle cryo-EM to explore the dynamic structures of other ABC transporters and molecular machines.

Keywords: ABC transporter; Mycobacterium smegmatis; carbon metabolism; cryo-EM.