Iron regulatory protein 1 (IRP1) is a dual-function protein. With an iron-sulfur cluster bound, it is a cytosolic aconitase enzyme, but without it, IRP1 binds iron-responsive elements (IREs) in messenger RNA and regulates the expression of genes involved in iron transport, storage, and utilization. Walden et al. now describe the structure of IRP1 bound to ferritin H IRE at 2.8 angstrom resolution and compare it with the known structure of cytosolic aconitase. The switch between the two functions is coupled to large-scale domain rearrangements, from a compact structure in the aconitase to an extended structure that interacts with the IRE at two sites. The RNA binding and enzyme active sites overlap with many amino acids that serve different roles in each state.
W. E. Walden, A. I. Selezneva, J. Dupuy, A. Volbeda, J. C. Fontecilla-Camps, E. C. Theil, K. Volz, Structure of dual function iron regulatory protein 1 complexed with ferritin IRE-RNA. Science 314, 1903-1908 (2006). [Abstract] [Full Text]