Correction: Extracellular loops of BtuB facilitate transport of vitamin B12 through the outer membrane of E. coli
| Autor: | Joanna Trylska, Tomasz Pieńko |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
B Vitamins
0301 basic medicine Protein Folding Sucrose Lipid Bilayers Normal Distribution Crystallography X-Ray Molecular Dynamics Physical Chemistry Biochemistry Protein Structure Secondary chemistry.chemical_compound Computational Chemistry 0302 clinical medicine Antibiotics Biochemical Simulations Medicine and Health Sciences polycyclic compounds Biology (General) Crystallography Ecology biology Organic Compounds Antimicrobials Escherichia coli Proteins Physics Drugs Vitamins Condensed Matter Physics Lipids Anti-Bacterial Agents Vitamin B 12 Chemistry Computational Theory and Mathematics Modeling and Simulation Physical Sciences Periplasm Cobalamin binding Crystal Structure Umbrella sampling Bacterial outer membrane Algorithms Bacterial Outer Membrane Proteins Protein Binding Research Article QH301-705.5 Cobalamin transport Heme Molecular Dynamics Simulation Microbiology Cobalamin Cofactor Cobalamins 03 medical and health sciences Cellular and Molecular Neuroscience Protein Domains Microbial Control Escherichia coli Genetics Extracellular Solid State Physics Molecular Biology Ecology Evolution Behavior and Systematics Ions Pharmacology Binding Sites Chemical Bonding Organic Chemistry Chemical Compounds Correction Membrane Proteins Membrane Transport Proteins Water Biology and Life Sciences Computational Biology nutritional and metabolic diseases Hydrogen Bonding Periplasmic space 030104 developmental biology chemistry Biophysics biology.protein 030217 neurology & neurosurgery |
| Zdroj: | PLoS Computational Biology PLoS Computational Biology, Vol 16, Iss 7, p e1008024 (2020) |
| ISSN: | 1553-7358 |
| DOI: | 10.1371/journal.pcbi.1008024 |
| Popis: | Vitamin B12 (or cobalamin) is an enzymatic cofactor essential both for mammals and bacteria. However, cobalamin can be synthesized only by few microorganisms so most bacteria need to take it up from the environment through the TonB-dependent transport system. The first stage of cobalamin import to E. coli cells occurs through the outer-membrane receptor called BtuB. Vitamin B12 binds with high affinity to the extracellular side of the BtuB protein. BtuB forms a β-barrel with inner luminal domain and extracellular loops. To mechanically allow for cobalamin passage, the luminal domain needs to partially unfold with the help of the inner-membrane TonB protein. However, the mechanism of cobalamin permeation is unknown. Using all-atom molecular dynamics, we simulated the transport of cobalamin through the BtuB receptor embedded in an asymmetric and heterogeneous E. coli outer-membrane. To enhance conformational sampling of the BtuB loops, we developed the Gaussian force-simulated annealing method (GF-SA) and coupled it with umbrella sampling. We found that cobalamin needs to rotate in order to permeate through BtuB. We showed that the mobility of BtuB extracellular loops is crucial for cobalamin binding and transport and resembles an induced-fit mechanism. Loop mobility depends not only on the position of cobalamin but also on the extension of luminal domain. We provided atomistic details of cobalamin transport through the BtuB receptor showing the essential role of the mobility of BtuB extracellular loops. A similar TonB-dependent transport system is used also by many other compounds, such as haem and siderophores, and importantly, can be hijacked by natural antibiotics. Our work could have implications for future delivery of antibiotics to bacteria using this transport system. Author summary Vitamin B12, also called cobalamin, is essential for mammalian and bacterial metabolism. However, only few microorganisms can synthesize vitamin B12 and in order to grow most bacteria need to retrieve it from the environment. Cobalamin uptake into E. coli first occurs through their outer-membrane protein called BtuB. The three-dimensional structure of BtuB has been resolved revealing that BtuB forms a β-barrel with inner luminal domain and extracellular loops. To mechanically enable cobalamin passage, luminal domain needs to partially unfold, but the detailed mechanism of cobalamin transport is still unknown. Using various molecular dynamics simulation techniques, we determined atomistic details of cobalamin transport through BtuB showing the mobility of BtuB extracellular loops during cobalamin binding and permeation. Our work implies future use of such transport systems to deliver antibiotics because a similar TonB-dependent transport system is used also by other compounds, such as haem and sucrose, and importantly, by natural antibiotics. Thus, our work can contribute to the development of delivery methods of antibiotics into bacteria. |
| Databáze: | OpenAIRE |
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