Mechanistic Picture for Chemomechanical Coupling in a Bacterial Proton-Coupled Oligopeptide Transporter from Streptococcus Thermophilus.
Kalyan ImmadisettyMahmoud MoradiPublished in: The journal of physical chemistry. B (2021)
Proton-coupled oligopeptide transporters (POTs) use the proton electrochemical gradient to transport peptides across the cell membrane. Despite the significant biological and biomedical relevance of these proteins, a detailed mechanistic picture for chemomechanical couplings involved in substrate/proton transport and protein structural changes is missing. Therefore, we performed microsecond-level molecular dynamics simulations of bacterial POT PepTSt, which shares ∼80% sequence identity with the human POT, PepT1, in the substrate-binding region. Three different conformational states of PepTSt were simulated, including (i) occluded, apo, (ii) inward-facing, apo, and (iii) inward-facingoccluded, Leu-Ala bound. We propose that the interaction of R33 with E299 and E300 acts as a conformational switch (i.e., to trigger the conformational change from an inward- to outward-facing state) in the substrate transport. Additionally, we propose that E299 and E400 disengage from interacting with the substrate either through protonation or through coordination with a cation for the substrate to get transported. This study provides clues to understand the chemomechanical couplings in POTs and paves the way to decipher the molecular-level underpinnings of the structure-function relationship in this important family of transporters.
Keyphrases
- molecular dynamics simulations
- amino acid
- molecular docking
- single molecule
- electron transfer
- molecular dynamics
- structural basis
- endothelial cells
- binding protein
- ionic liquid
- gold nanoparticles
- escherichia coli
- candida albicans
- biofilm formation
- pseudomonas aeruginosa
- protein protein
- protein kinase
- induced pluripotent stem cells