Probing the transport of Ni(II) ions through the internal tunnels of the Helicobacter pylori UreDFG multimeric protein complex

The survival of several pathogenic bacteria, such as Helicobacter pylori (Hp), relies on the activity of the nickel-dependent enzyme urease. Nickel insertion into urease is mediated by a multimeric chaperone complex (HpUreDFG) that is responsible for the transport of Ni(II) from a conserved metal binding motif located in the UreG dimer (CPH motif) to the catalytic site of the enzyme. The X-ray structure of HpUreDFG revealed the presence of water-filled tunnels that were proposed as a route for Ni(II) translocation. Here, we probe the transport of Ni(II) through the internal tunnels of HpUreDFG, from the CPH motif to the external surface of the complex, using microsecond-long enhanced molecular dynamics simulations. The results suggest a “bucket-brigade” mechanism whereby Ni(II) can be transported through a series of stations found along these internal pathways. [Display omitted] •Helicobacter pylori relies on the Ni(II)-dependent enzyme urease.•Ni(II) insertion into urease requires a multimeric chaperone complex (HpUreDFG).•HpUreDFG structure shows internal tunnels that can be involved in Ni(II) transport.•Ni(II) translocation was probed using μs-long enhanced MD simulations.•The results suggest that Ni(II) can be transported through a series of stations.