Inhibitor binding changes domain mobility in the iron–sulfur protein of the mitochondrial bc1 complex from bovine heart

We have analyzed crystal structures of cytochrome bc1 complexes with electron transfer inhibitors bound to the ubiquinone binding pockets Q(i) and/or Q(o) in the cytochrome b subunit. The presence or absence of the Q(i) inhibitor antimycin A did not affect the binding of the Q(o) inhibitors. Different subtypes of Q(o) inhibitors had dramatically different effects on the mobility of the extramembrane domain of the iron–sulfur protein (ISP): Binding of 5-undecyl-6-hydroxy-4,7-dioxobenzothiazol and stigmatellin (subtype Q(o)–II and Q(o)–III, respectively) led to a fixation of the ISP domain on the surface of cytochrome b, whereas binding of myxothiazol and methoxyacrylate-stilbene (subtype Q(o)–I) favored release of this domain. The native structure has an empty Q(o) pocket and is intermediate between these extremes. On the basis of these observations we propose a model of quinone oxidation in the bc1 complex, which incorporates fixed and loose states of the ISP as features important for electron transfer and, possibly, also proton transport.