The dynamics of the MBP-MalFGK(2) interaction: a prototype for binding protein dependent ABC-transporter systems.

This review is focused on the interaction between maltose binding protein (MBP) and the maltose transporter complex, MalFGK(2), which is a member of the ATP Binding Cassette (ABC) superfamily. The interaction between MBP and MalFGK(2) has a critical role in maltose transport, but a coherent description of the interaction is complicated because both MBP and MalFGK(2) can adopt multiple conformations. Drawing on genetic, structural, and biochemical data, the different conformations of MBP and MalFGK(2) are described and incorporated into a model for their interaction. The most important feature of this model is that ligand-bound MBP initiates the process of ATP-dependent maltose transport by stabilizing a high-energy conformation of MalFGK(2). In this model of the MBP-MalFGK(2) interaction, stabilization of a high-energy conformation of MalFGK(2) allows ATP to drive conformational changes in the system - in particular the opening of bound MBP - that leads to formation of a transition state for ATP hydrolysis. Such a role for ligand-bound MBP explains how MBP-independent MalFGK(2) mutants work, and represents a general mechanism for binding-protein dependent ABC import systems. In ABC export systems, which do not use a binding protein, the substrate itself is expected to play a role similar to ligand-bound MBP in the maltose transport system. The mechanistic model for the maltose transporter suggests that ABC-type import systems evolved to make use of a peripheral binding protein so that the transport process is essentially irreversible.