Mycobacterial dynamin-like protein IniA mediates membrane fission

Nat Commun. 2019 Aug 29;10(1):3906. doi: 10.1038/s41467-019-11860-z.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Cell Membrane / metabolism*
  • Cloning, Molecular
  • Crystallography, X-Ray
  • Drug Resistance, Multiple, Bacterial
  • Dynamins / chemistry*
  • Dynamins / genetics
  • Dynamins / metabolism*
  • GTP Phosphohydrolases / metabolism
  • Gene Expression Regulation, Bacterial
  • Genes, Bacterial
  • Humans
  • Membrane Fusion / physiology*
  • Models, Molecular
  • Mycobacterium smegmatis / metabolism*
  • Protein Conformation
  • Protein Domains

Substances

  • GTP Phosphohydrolases
  • Dynamins