Abstract

Mycobacterium tuberculosis infection remains a major threat to human health worldwide. Drug treatments against tuberculosis (TB) induce expression of several mycobacterial proteins, including IniA, but its structure and function remain poorly understood. Here, we report the structures of Mycobacterium smegmatis IniA in both the nucleotide-free and GTP-bound states. The structures reveal that IniA folds as a bacterial dynamin-like protein (BDLP) with a canonical GTPase domain followed by two helix-bundles (HBs), named Neck and Trunk. The distal end of its Trunk domain exists as a lipid-interacting (LI) loop, which binds to negatively charged lipids for membrane attachment. IniA does not form detectable nucleotide-dependent dimers in solution. However, lipid tethering indicates nucleotide-independent association of IniA on the membrane. IniA also deforms membranes and exhibits GTP-hydrolyzing dependent membrane fission. These results confirm the membrane remodeling activity of BDLP and suggest that IniA mediates TB drug-resistance through fission activity to maintain plasma membrane integrity.

Details

Title
Mycobacterial dynamin-like protein IniA mediates membrane fission
Author
Wang, Manfu 1 ; Guo, Xiangyang 2   VIAFID ORCID Logo  ; Yang, Xiuna 3 ; Zhang, Bing 3 ; Ren, Jie 4 ; Liu, Aijun 5 ; Ran, Yajun 3 ; Yan, Bing 4 ; Chen, Fang 4 ; Guddat, Luke W 6 ; Hu, Junjie 7   VIAFID ORCID Logo  ; Li, Jun 3 ; Rao, Zihe 8 

1  Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai, China; CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China; University of Chinese Academy of Sciences, Beijing, China 
2  State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, and Tianjin Key Laboratory of Protein Sciences, Tianjin, China 
3  Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai, China; CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China 
4  National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Science, Beijing, China 
5  Laboratory of Structural Biology, School of Medicine, Tsinghua University, Beijing, China 
6  School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD, Australia 
7  State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, and Tianjin Key Laboratory of Protein Sciences, Tianjin, China; National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Science, Beijing, China 
8  Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai, China; State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, and Tianjin Key Laboratory of Protein Sciences, Tianjin, China; National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Science, Beijing, China; Laboratory of Structural Biology, School of Medicine, Tsinghua University, Beijing, China 
Pages
1-13
Publication year
2019
Publication date
Aug 2019
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-019-11860-z
ProQuest document ID
2282440172
Copyright
© 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.