The mechanism of nucleotide-binding domain dimerization in the intact maltose transporter as studied by all-atom molecular dynamics simulations

摘要

The Escherichia coli maltose transporter MalFGK(2)-E belongs to the protein superfamily of ATP-binding cassette (ABC) transporters. This protein is composed of heterodimeric transmembrane domains (TMDs) MalF and MalG, and the homodimeric nucleotide-binding domains (NBDs) MalK(2). In addition to the TMDs and NBDs, the periplasmic maltose binding protein MalE captures maltose and shuttle it to the transporter. In this study, we performed all-atom molecular dynamics (MD) simulations on the maltose transporter and found that both the binding of MalE to the periplasmic side of the TMDs and binding of ATP to the MalK(2) are necessary to facilitate the conformational change from the inward-facing state to the occluded state, in which MalK(2) is completely dimerized. MalE binding suppressed the fluctuation of the TMDs and MalF periplasmic region (MalF-P2), and thus prevented the incorrect arrangement of the MalF C-terminal (TM8) helix. Without MalE binding, the MalF TM8 helix showed a tendency to intrude into the substrate translocation pathway, hindering the closure of the MalK(2). This observation is consistent with previous mutagenesis experimental results on MalF and provides a new point of view regarding the understanding of the substrate translocation mechanism of the maltose transporter.