The binding interface of cytochrome c and cytochrome c1 in the bc1 complex: Rationalizing the role of key residues

Oleksandr Kokhan, Colin A. Wraight, Emad Tajkhorshid

Research output: Contribution to journalArticlepeer-review

Abstract

The interaction of cytochrome c with ubiquinol-cytochrome c oxidoreductase (bc1 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-bc1 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-c1 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 proteinprotein 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 1 monomers responsible for limiting the binding of cyt c to only one molecule per bc1 dimer by altering the affinity of the cytochrome c binding site on the second cyt c1 monomer.

Original languageEnglish (US)
Pages (from-to)2647-2656
Number of pages10
JournalBiophysical journal
Volume99
Issue number8
DOIs
StatePublished - Oct 20 2010

ASJC Scopus subject areas

  • Biophysics

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