Letter | Published:

Structural basis for lipopolysaccharide insertion in the bacterial outer membrane

Nature volume 511, pages 108111 (03 July 2014) | Download Citation

Abstract

One of the fundamental properties of biological membranes is the asymmetric distribution of membrane lipids. In Gram-negative bacteria, the outer leaflet of the outer membrane is composed predominantly of lipopolysaccharides (LPS)1. The export of LPS requires seven essential lipopolysaccharide transport (Lpt) proteins to move LPS from the inner membrane, through the periplasm to the surface2. Of the seven Lpt proteins, the LptD–LptE complex is responsible for inserting LPS into the external leaflet of the outer membrane3,4. Here we report the crystal structure of the 110-kilodalton membrane protein complex LptD–LptE from Shigella flexneri at 2.4 Å resolution. The structure reveals an unprecedented two-protein plug-and-barrel architecture with LptE embedded into a 26-stranded β-barrel formed by LptD. Importantly, the secondary structures of the first two β-strands are distorted by two proline residues, weakening their interactions with neighbouring β-strands and creating a potential portal on the barrel wall that could allow lateral diffusion of LPS into the outer membrane. The crystal structure of the LptD–LptE complex opens the door to new antibiotic strategies targeting the bacterial outer membrane.

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Protein Data Bank

Data deposits

The coordinates and diffraction data of the LptD–LptE complex crystal structure have been deposited in the Protein Data Bank with the accession code 4Q35.

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Acknowledgements

The authors thank Y. Shan for discussions, H. Wu, J. Deisenhofer, Y. Jiang, N. Huang, Z. Zhou, G. Li, Z. Liu and members of the Huang group for critically reading the manuscript. The diffraction data were collected at the Shanghai Synchrotron Radiation Facility (SSRF, China) and Beijing Synchrotron Radiation Facility of China (BSRF, China). This work was supported by grants from the Ministry of Science and Technology (2012CB917302 and 2013CB910603 to Y.H.), the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB080203 to Y.H. and X.C.Z.) and the National Natural Science Foundation of China (31170698 to Y.H.).

Author information

Affiliations

  1. National Laboratory of Biomacromolecules, National Center of Protein Science-Beijing, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China

    • Shuai Qiao
    • , Qingshan Luo
    • , Yan Zhao
    • , Xuejun Cai Zhang
    •  & Yihua Huang
  2. University of Chinese Academy of Sciences, Beijing 100101, China

    • Shuai Qiao
    •  & Qingshan Luo
  3. School of Life Sciences, University of Science and Technology of China, Hefei 230027, Anhui, China

    • Yan Zhao

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Contributions

Y.H. supervised the project. S.Q. and Q.L. performed the experiments. S.Q., Y.Z. and Y.H. collected diffraction data. Y.H. built the model and refined the structure. Y.H., X.C.Z., S.Q. and Y.Z. contributed to manuscript preparation. Y.H. wrote the manuscript. All authors contributed to data analysis. Correspondence and material request should be address to Yihua Huang. The authors declare no competing financial interests.

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The authors declare no competing financial interests.

Corresponding author

Correspondence to Yihua Huang.

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https://doi.org/10.1038/nature13484

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