Question

How is ATP hydrolysis coupled to transporter conformational changes? Please show a drawing and explanation.

Answer 1

ABC transporters constitute one of the largest protein superfamilies in all organisms . They share a common building block, namely the ATP-binding cassette that binds and hydrolyzes ATP. The released energy is utilized to uni-directionally transport substrate across cell membranes. ABC importers are often involved in nutrient uptake, pathogenicity and virulence , whereas ABC exporters are associated with lipid transport, multidrug resistance and genetic diseases . ABC transporters minimally consist of four domains, including two transmembrane domains (TMDs) and two ATP-binding cassettes (also called nucleotide-binding domains, NBDs)

In the periplasmic binding protein-dependent transport systems, the soluble binding protein is the first component to interact with the substrate to be transported, acting as a high-affinity receptor for the substrate in the periplasm (see Fig). Interaction of the ligand-bound binding protein with the transporter stimulates the ATPase activity of the transporter and initiates transport. A fuller understanding of how these binding proteins function in transport was realized following our recent observation in the maltose transport system that the periplasmic maltose binding protein (MBP) becomes tightly bound to the membrane transporter (MalFGK₂, a complex of MalF, MalG, and two MalK proteins) in the presumed catalytic transition state for ATP hydrolysis In the transition state conformation, the affinity of the binding protein for maltose is reduced and the sugar is presumably transferred to the transporter and ultimately into the cell.

Example:

Model for maltose transport. (A) MBP binds maltose, undergoing a change from an open conformation to a closed conformation, generating a high-affinity sugar-binding site. In the closed conformation, MBP binds MalFGK₂ to initiate transport and hydrolysis. (B) In the transition state for ATP hydrolysis, MBP becomes tightly bound to MalFGK₂, and internal sugar-binding sites are exposed to each other. This opening of MBP in the transition state reduces the affinity of MBP for maltose, facilitating the transfer of sugar to MalFGK₂. (C) Maltose is transported, and MBP is released after reexposure of the membrane-binding site to the cytoplasm. MBP activates the ATPase activity of MalK by bringing the two MalK subunits into close proximity, completing the nucleotide-binding site(s) at the MalK-MalK interface with residues donated from the opposing subunit.