The binding interface of cytochrome c and cytochrome c? in the bc? complex: rationalizing the role of key residues.

ABSTRACT: The interaction of cytochrome c with ubiquinol-cytochrome c oxidoreductase (bc? complex) has been studied for >30 years, yet many aspects remain unclear or controversial. We report the first molecular dynamic simulations of the cyt c-bc? complex interaction. Contrary to the results of crystallographic studies, our results show that there are multiple dynamic hydrogen bonds and salt bridges in the cyt c-c? interface. These include most of the basic cyt c residues previously implicated in chemical modification studies. We suggest that the static nature of x-ray structures can obscure the quantitative significance of electrostatic interactions between highly mobile residues. This provides a clear resolution of the discrepancy between the structural data and functional studies. It also suggests a general need to consider dynamic interactions of charged residues in protein-protein interfaces. In addition, a novel structural change in cyt c is reported, involving residues 21-25, which may be responsible for cyt c destabilization upon binding. We also propose a mechanism of interaction between cyt c? monomers responsible for limiting the binding of cyt c to only one molecule per bc? dimer by altering the affinity of the cytochrome c binding site on the second cyt c? monomer.

SUBMITTER: Kokhan O 

PROVIDER: S-EPMC2955499 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature