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 e lectron 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 Qi inhibitor antimycin A did not affect the binding of the Q(o) i nhibitors. Different subtypes of Q(o) inhibitors had dramatically diff erent effects on the mobility of the extramembrane domain of the iron- sulfur protein (ISP): Binding of 5-undecyl-6-hydroxy-4,7-dioxobenzothi azol 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, where as 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 featu res important for electron transfer and, possibly, also proton transpo rt.