Mapping the surface of MNKr2 and CopZ - identification of residues critical for metallotransfer

Full text: Cells utilise a network of proteins that include CPx-type ATPases and metallochaperones to balance intracellular copper concentration. The Menkes ATPase has six N-terminal domains which bind Cu(I) and are critical for ATPase function. The NMR solution structure of the second domain (MNKr2) shows that the structure adopts an 'open-faced β-sandwich' fold, in which two α-helices lie over a single four stranded β-sheet. The global fold is identical to the bacterial copper chaperone CopZ MNKr2 is unable to substitute for CopZ in copper transfer to the cop operon represser, CopY. To investigate how structure affects function we have analysed the surface features of MNKr2 and CopZ Despite having the same global fold, MNKr2 and CopZ have contrasting electrostatic surfaces, which may partially explain the inability of MNKr2 to transfer copper to CopY