Mycobacterial dynamin-like protein IniA mediates membrane fission.

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

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
29 08 2019
Historique:
received: 08 05 2018
accepted: 24 07 2019
entrez: 31 8 2019
pubmed: 31 8 2019
medline: 7 1 2020
Statut: epublish

Résumé

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.

Identifiants

DOI: 10.1038/s41467-019-11860-z PMID: 31467269 PMC: PMC6715688
pubmed: 31467269
doi: 10.1038/s41467-019-11860-z
pii: 10.1038/s41467-019-11860-z
pmc: PMC6715688
doi:

Substances chimiques

GTP Phosphohydrolases EC 3.6.1.-
Dynamins EC 3.6.5.5

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

3906

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Auteurs

Manfu Wang (M)

Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China.
CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, 200031, China.
University of Chinese Academy of Sciences, Beijing, 100101, China.

Xiangyang Guo (X)

State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, and Tianjin Key Laboratory of Protein Sciences, Tianjin, 300071, China.
ORCID: 0000-0002-8463-2755

Xiuna Yang (X)

Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China.
CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, 200031, China.

Bing Zhang (B)

Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China.
CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, 200031, China.

Jie Ren (J)

National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Science, Beijing, 100101, China.

Aijun Liu (A)

Laboratory of Structural Biology, School of Medicine, Tsinghua University, Beijing, 100084, China.

Yajun Ran (Y)

Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China.
CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, 200031, China.

Bing Yan (B)

National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Science, Beijing, 100101, China.

Fang Chen (F)

National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Science, Beijing, 100101, China.

Luke W Guddat (LW)

School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, 4072, QLD, Australia.

Junjie Hu (J)

State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, and Tianjin Key Laboratory of Protein Sciences, Tianjin, 300071, China. huj@ibp.ac.cn.
National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Science, Beijing, 100101, China. huj@ibp.ac.cn.
ORCID: 0000-0003-4712-2243

Jun Li (J)

Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China. lijun@sibcb.ac.cn.
CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, 200031, China. lijun@sibcb.ac.cn.

Zihe Rao (Z)

Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China.
State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, and Tianjin Key Laboratory of Protein Sciences, Tianjin, 300071, China.
National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Science, Beijing, 100101, China.
Laboratory of Structural Biology, School of Medicine, Tsinghua University, Beijing, 100084, China.

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Classifications MeSH

questionsmedicales.fr › Phénomènes chimiques › Phénomènes biochimiques › Sites de fixation › Mycobacterial dynamin-like protein IniA...
questionsmedicales.fr › Cellules › Structures cellulaires › Membrane cellulaire › Mycobacterial dynamin-like protein IniA...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Clonage moléculaire › Mycobacterial dynamin-like protein IniA...
questionsmedicales.fr › Techniques d'investigation › Techniques de chimie analytique › Cristallographie aux rayons X › Mycobacterial dynamin-like protein IniA...
questionsmedicales.fr › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes pharmacologiques › Résistance aux substances › Multirésistance aux médicaments › Multirésistance bactérienne aux médicaments › Mycobacterial dynamin-like protein IniA...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Protéines du transport vésiculaire › Dynamines › Mycobacterial dynamin-like protein IniA...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Hydrolases › Acid anhydride hydrolases › dGTPases › Mycobacterial dynamin-like protein IniA...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Régulation de l'expression des gènes bactériens › Mycobacterial dynamin-like protein IniA...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Génome microbien › Génome bactérien › Gènes bactériens › Mycobacterial dynamin-like protein IniA...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Mycobacterial dynamin-like protein IniA...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Fusion membranaire › Mycobacterial dynamin-like protein IniA...
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles moléculaires › Mycobacterial dynamin-like protein IniA...
questionsmedicales.fr › Bactéries › Bactéries à Gram positif › Bâtonnets à Gram positif › Bâtonnets asporogènes à Gram positif › Bâtonnets asporogènes réguliers à Gram positif › Mycobacteriaceae › Mycobacterium › Mycobactéries non tuberculeuses › Mycobacterium smegmatis › Mycobacterial dynamin-like protein IniA...
questionsmedicales.fr › Phénomènes chimiques › Phénomènes biochimiques › Conformation moléculaire › Conformation des protéines › Mycobacterial dynamin-like protein IniA...
questionsmedicales.fr › Phénomènes chimiques › Phénomènes biochimiques › Conformation moléculaire › Conformation des protéines › Structure tertiaire des protéines › Domaines protéiques › Mycobacterial dynamin-like protein IniA...