6J72

Crystal structure of IniA from Mycobacterium smegmatis with GTP bound

Summary for 6J72

• Entry DOI: 10.2210/pdb6j72/pdb
• Descriptor: Isoniazid inducible gene protein IniA, GUANOSINE-5'-TRIPHOSPHATE, MAGNESIUM ION, ... (5 entities in total)
• Functional Keywords: gtpase, dynamin-like, drug-resistance, hydrolase
• Biological source: Mycolicibacterium smegmatis MC2 155
• Total number of polymer chains: 1
• Total formula weight: 67283.11

Authors

Wang, M.F.,Guo, X.Y.,Hu, J.J.,Li, J.,Rao, Z.H. (deposition date: 2019-01-16, release date: 2019-09-11, Last modification date: 2024-03-27)

Primary citation

Wang, M.,Guo, X.,Yang, X.,Zhang, B.,Ren, J.,Liu, A.,Ran, Y.,Yan, B.,Chen, F.,Guddat, L.W.,Hu, J.,Li, J.,Rao, Z.
Mycobacterial dynamin-like protein IniA mediates membrane fission.
Nat Commun, 10:3906-3906, 2019

PubMed 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.

PubMed: 31467269
DOI: 10.1038/s41467-019-11860-z

Experimental method

X-RAY DIFFRACTION (2.2 Å)