TCB Publications - Abstract

O. Kokhan, C. Wraight, and E. Tajkhorshid. The binding interface of cytochrome c and cytochrome c1 in the bc1 complex: rationalizing the role of key residues. Biophysical Journal, 99:2647-2656, 2010.

KOKH2010-ET The interaction of cytochrome c with ubiquinol-cytochrome c oxidoreductase ( bc$_{1}$ 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$_{1}$ 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$_{1}$ 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 2125, which may be responsible for cyt c destabilization upon binding. We also propose a mechanism of interaction between cyt c$_{1}$ monomers responsible for limiting the binding of cyt c to only one molecule per bc$_{1}$ dimer by altering the affinity of the cytochrome c binding site on the second cyt c$_{1}$ monomer.

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