Cell Reports (Oct 2020)
Structural and Functional Insights into an Archaeal Lipid Synthase
- Sixue Ren,
- Niels A.W. de Kok,
- Yijun Gu,
- Weizhu Yan,
- Qiu Sun,
- Yunying Chen,
- Jun He,
- Lejin Tian,
- Ruben L.H. Andringa,
- Xiaofeng Zhu,
- Mei Tang,
- Shiqian Qi,
- Heng Xu,
- Haiyan Ren,
- Xianghui Fu,
- Adriaan J. Minnaard,
- Shengyong Yang,
- Wanjiang Zhang,
- Weimin Li,
- Yuquan Wei,
- Arnold J.M. Driessen,
- Wei Cheng
Affiliations
- Sixue Ren
- Division of Respiratory and Critical Care Medicine, Respiratory Infection and Intervention Laboratory of Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu 610041, China
- Niels A.W. de Kok
- Department of Molecular Microbiology, Groningen Biomolecular Sciences and Biotechnology Institute, and The Zernike Institute for Advanced Materials, University of Groningen, Nijenborgh 7, 9747 AG Groningen, the Netherlands
- Yijun Gu
- National Facility for Protein Science Shanghai, Shanghai Synchrotron Radiation Facility, Shanghai Advanced Research Institute (Zhangjiang Lab), Zhangheng Road 239, Shanghai 201203, China
- Weizhu Yan
- Division of Respiratory and Critical Care Medicine, Respiratory Infection and Intervention Laboratory of Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu 610041, China
- Qiu Sun
- Division of Respiratory and Critical Care Medicine, Respiratory Infection and Intervention Laboratory of Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu 610041, China
- Yunying Chen
- Division of Respiratory and Critical Care Medicine, Respiratory Infection and Intervention Laboratory of Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu 610041, China
- Jun He
- Division of Respiratory and Critical Care Medicine, Respiratory Infection and Intervention Laboratory of Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu 610041, China
- Lejin Tian
- Division of Respiratory and Critical Care Medicine, Respiratory Infection and Intervention Laboratory of Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu 610041, China
- Ruben L.H. Andringa
- Stratingh Institute for Chemistry, University of Groningen, Nijenborgh 7, 9747 AG Groningen, the Netherlands
- Xiaofeng Zhu
- Division of Respiratory and Critical Care Medicine, Respiratory Infection and Intervention Laboratory of Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu 610041, China
- Mei Tang
- Division of Respiratory and Critical Care Medicine, Respiratory Infection and Intervention Laboratory of Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu 610041, China
- Shiqian Qi
- Division of Respiratory and Critical Care Medicine, Respiratory Infection and Intervention Laboratory of Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu 610041, China
- Heng Xu
- Division of Respiratory and Critical Care Medicine, Respiratory Infection and Intervention Laboratory of Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu 610041, China
- Haiyan Ren
- Division of Respiratory and Critical Care Medicine, Respiratory Infection and Intervention Laboratory of Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu 610041, China
- Xianghui Fu
- Division of Respiratory and Critical Care Medicine, Respiratory Infection and Intervention Laboratory of Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu 610041, China
- Adriaan J. Minnaard
- Stratingh Institute for Chemistry, University of Groningen, Nijenborgh 7, 9747 AG Groningen, the Netherlands
- Shengyong Yang
- Division of Respiratory and Critical Care Medicine, Respiratory Infection and Intervention Laboratory of Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu 610041, China
- Wanjiang Zhang
- Department of Pathophysiology, Shihezi University School of Medicine, the Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Shihezi, Xinjiang 832002, China
- Weimin Li
- Division of Respiratory and Critical Care Medicine, Respiratory Infection and Intervention Laboratory of Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu 610041, China
- Yuquan Wei
- Division of Respiratory and Critical Care Medicine, Respiratory Infection and Intervention Laboratory of Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu 610041, China
- Arnold J.M. Driessen
- Department of Molecular Microbiology, Groningen Biomolecular Sciences and Biotechnology Institute, and The Zernike Institute for Advanced Materials, University of Groningen, Nijenborgh 7, 9747 AG Groningen, the Netherlands; Corresponding author
- Wei Cheng
- Division of Respiratory and Critical Care Medicine, Respiratory Infection and Intervention Laboratory of Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu 610041, China; Corresponding author
- Journal volume & issue
-
Vol. 33,
no. 3
p. 108294
Abstract
Summary: The UbiA superfamily of intramembrane prenyltransferases catalyzes an isoprenyl transfer reaction in the biosynthesis of lipophilic compounds involved in cellular physiological processes. Digeranylgeranylglyceryl phosphate (DGGGP) synthase (DGGGPase) generates unique membrane core lipids for the formation of the ether bond between the glycerol moiety and the alkyl chains in archaea and has been confirmed to be a member of the UbiA superfamily. Here, the crystal structure is reported to exhibit nine transmembrane helices along with a large lateral opening covered by a cytosolic cap domain and a unique substrate-binding central cavity. Notably, the lipid-bound states of this enzyme demonstrate that the putative substrate-binding pocket is occupied by the lipidic molecules used for crystallization, indicating the binding mode of hydrophobic substrates. Collectively, these structural and functional studies provide not only an understanding of lipid biosynthesis by substrate-specific lipid-modifying enzymes but also insights into the mechanisms of lipid membrane remodeling and adaptation.
