Mycobacterial dynamin-like protein IniA mediates membrane fission
Manfu Wang, Xiangyang Guo, Xiuna Yang, Bing Zhang, Jie Ren, Aijun Liu, Yajun Ran, Bing Yan, Fang Chen, Luke W. Guddat, Junjie Hu, Jun Li & Zihe Rao
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.
附件下载：
Mycobacterial dynamin-like protein IniA mediates membrane fission, Nature Comm, 29 Aug 2019
Nature Communications, 29 August, 2019，DOI：https://doi.org/10.1038/s41467-019-11860-z
Mycobacterial dynamin-like protein IniA mediates membrane fission
Manfu Wang, Xiangyang Guo, Xiuna Yang, Bing Zhang, Jie Ren, Aijun Liu, Yajun Ran, Bing Yan, Fang Chen, Luke W. Guddat, Junjie Hu, Jun Li & Zihe Rao
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.
文章链接：https://www.nature.com/articles/s41467-019-11860-z
相关报道：http://www.ibp.cas.cn/kyjz/zxdt/201908/t20190830_5373894.html