Details Define Double Duty

Science  22 Dec 2006:
Vol. 314, Issue 5807, pp. 1837j
DOI: 10.1126/science.314.5807.1837j

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. (p. 1903; see the Perspective by Rouault) 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.

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