title: Unveiling the gating mechanism of ECF transporter RibU.
abstract: Energy-coupling factor (ECF) transporters are responsible for uptake of micronutrients in prokaryotes. The recently reported crystal structure of an ECF transporter RibU provided a foundation for understanding the structure and transport mechanism of ECF transporters. In the present study, molecular dynamics (MD) was carried out to study the conformational changes of the S component RibU upon binding by riboflavin. Our result and analysis revealed a critically important gating mechanism, in which part of loop5 (L5') (eleven residues, missing in the crystal structure) between TM5 and TM6 is dynamically flexible and serves as a gate. Specifically, the L5' opens a large cavity accessible to riboflavin from the extracellular space in Apo-RibU and closes the cavity upon riboflavin binding through hydrophobic packing with riboflavin. Thus, L5'is proposed to be the gate for riboflavin binding. In addition, steered molecular dynamics (SMD) simulation is employed to investigate the translocation dynamics of RibU during riboflavin transport. The simulation result does not show evidence that the S component alone can carry out the transport function. Since loop regions are very flexible and therefore could not be resolved by crystallography, their dynamics are hard to predict based on crystal structure alone.
authors.affiliation: State Key Laboratory of Precision Spectroscopy, Department of Physics, Institute of Theoretical and Computational Science, East China Normal University, Shanghai 200062, China.
authors.forename: Jianing
authors.initials: J
authors.lastname: Song
authors.affiliation: 1] State Key Laboratory of Precision Spectroscopy, Department of Physics, Institute of Theoretical and Computational Science, East China Normal University, Shanghai 200062, China [2] Institutes for Advanced Interdisciplinary Research, East China Normal University, Shanghai 200062, China [3] NYU-ECNU Center for Computational Chemistry at NYU Shanghai, Shanghai, China 200062.
authors.forename: Changge
authors.initials: C
authors.lastname: Ji
authors.affiliation: 1] State Key Laboratory of Precision Spectroscopy, Department of Physics, Institute of Theoretical and Computational Science, East China Normal University, Shanghai 200062, China [2] Institutes for Advanced Interdisciplinary Research, East China Normal University, Shanghai 200062, China [3] NYU-ECNU Center for Computational Chemistry at NYU Shanghai, Shanghai, China 200062.
authors.forename: John Z H
authors.initials: JZ
authors.lastname: Zhang
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000378:metabolism; D001665:Binding Sites; D001692:Biological Transport; D018360:Crystallography, X-Ray; D057927:Hydrophobic and Hydrophilic Interactions; D026901:Membrane Transport Proteins / Q000378:metabolism* / Q000648:ultrastructure; D056004:Molecular Dynamics Simulation; D011387:Prokaryotic Cells / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012256:Riboflavin / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D026901:Membrane Transport Proteins; D012256:Riboflavin