Models for the Metal Transfer Complex of the N-Terminal Region of CusB and CusF.

The tripartite CusCFBA pump in Escherichia coli is a very effective heavy metal extrusion system specific for Cu(I) and Ag(I). The N-terminal region of the membrane fusion protein CusB (CusB-NT) is highly disordered, and hence, experimentally characterizing its structure is challenging. In a previous study, this disorder was confirmed with molecular dynamics simulations, although some key structural elements were determined. It was experimentally shown that CusB-NT is fully functional in transferring the metal from the metallochaperone CusF. In this study, we docked these two entities together and formed two representative metal coordination modes, which consist of residues from both proteins. In this way, we created two potential CusB-NT/CusF complexes that share coordination of Cu(I) and thereby represent structural models for the metal transfer process. Each model complex was simulated for 4 μs. The previously observed structural disorder in CusB-NT disappeared upon complexation with CusF. The only dif...