The dynamics of the MBP–MalFGK 2 interaction: A prototype for binding protein dependent ABC-transporter systems

Abstract

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.