Mycobacterial dynamin-like protein IniA mediates membrane fission.
Manfu WangXiangyang GuoXiuna YangBing ZhangJie RenAijun LiuYajun RanBing YanFang ChenLuke W GuddatJunjie HuJun LiZihe RaoPublished in: Nature communications (2019)
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.
Keyphrases
- mycobacterium tuberculosis
- human health
- pulmonary tuberculosis
- risk assessment
- poor prognosis
- high resolution
- emergency department
- long non coding rna
- climate change
- mass spectrometry
- gene expression
- lower limb
- minimally invasive
- transcription factor
- dna methylation
- human immunodeficiency virus
- solid state
- hiv infected