Search

Sprouty proteins act as intracellular inhibitors of receptor tyrosine kinase signaling. Here we show that the mammalian Sprouty2 protein contains an iron-sulfur complex that can exist in an oxidized, reduced, or nitrosylated state. Purified Sprouty2 assembles into large monodisperse spheres containing approximately 24 polypeptides per particle. Biochemical experiments indicate that the charge state of the iron within Sprouty2 particles may be insulated from ambient intracellular redox. These features offer the possibility that Sprouty2 particles are capable of receiving, maintaining, and dissipating electrical charge in a manner formally equivalent to a battery.

The structure of activated pig heart aconitase [citrate(isocitrate) hydro-lyase, EC 4.2.1.3] containing a [4Fe-4S] cluster has been refined at 2.5-A resolution to a crystallographic residual of 18.2%. Comparison of this structure to the recently determined 2.1-A resolution structure of the inactive enzyme containing a [3Fe-4S] cluster, by difference Fourier analysis, shows that upon activation iron is inserted into the structure isomorphously. The common atoms of the [3Fe-4S] and [4Fe-4S] cores agree within 0.1 A; the three common cysteinyl S gamma ligand atoms agree within 0.25 A. The fourth ligand of the Fe inserted into the [3Fe-4S] cluster is a water or hydroxyl from solvent, consistent with the absence of a free cysteine ligand in the enzyme active site cleft and the isomorphism of the two structures. A water molecule occupies a similar site in the crystal structure of the inactive enzyme.