Anion size modulates the structure of the a state of cytochrome c

Several studies have shown that anions induce collapse of acid-denatured cy tochrome c into the compact A state having the properties of the molten glo bule and that the anion charge is the main determinant for the A state stab ilization. The results here reported show that the anion size plays a role in determining the overall structure of the A state. In particular, small a nions induce formation of an A state in which the native Met80-Fe(III) axia l bond is recovered and the nativelike redox properties restored. On the ot her hand, the A state stabilized by large anions shows a histidine (His26 o r His33) as the sixth ligand of the heme-iron, a very weak interaction betw een Trp59 and the heme propionate, and lacks nativelike redox properties. T he two anion-stabilized states show similar stability, indicating that (i) the hydrophobic core (which is equally stabilized by all the anions investi gated, independently of their size) is the region that mainly contributes t o the macromolecule stabilization, and (ii) the flexible loops are responsi ble for the spectroscopic (and, thus, structural) and redox differences obs erved.