Extracellular loops of BtuB facilitate transport of vitamin B12 through the outer membrane of E. coli

• DOI: 10.1371/journal.pcbi.1008024
• Publication Date: 2020-07-01T17:40:56Z
• Authors: Tomasz Pieńko; Joanna Trylska
• Keywords: Protein Folding; Sucrose; QH301-705.5; Lipid Bilayers; Normal Distribution; Heme; Molecular Dynamics Simulation; Crystallography, X-Ray; Protein Structure, Secondary; 03 medical and health sciences; Protein Domains; 11. Sustainability; Escherichia coli; Biology (General); Ions; 0303 health sciences; Binding Sites; Escherichia coli Proteins; Computational Biology; Membrane Proteins; Membrane Transport Proteins; Anti-Bacterial Agents; Algorithms; Research Article; Bacterial Outer Membrane Proteins; Protein Binding

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 TonB-dependent transport system. The first stage of import E. coli cells occurs outer-membrane receptor called BtuB. binds with high affinity extracellular side BtuB protein. forms a β-barrel inner luminal domain loops. To mechanically allow passage, needs partially unfold help inner-membrane TonB mechanism permeation unknown. Using all-atom molecular dynamics, we simulated embedded in asymmetric heterogeneous outer-membrane. enhance conformational sampling loops, developed Gaussian force-simulated annealing method (GF-SA) coupled umbrella sampling. We found that rotate order permeate showed mobility loops crucial binding resembles induced-fit mechanism. Loop depends not on position but also extension domain. provided atomistic details showing role A similar system used many other compounds, such as haem siderophores, importantly, hijacked natural antibiotics. Our work could have implications future delivery antibiotics using this