The binding interface of cytochrome c and cytochrome c₁ in the bc₁ complex: rationalizing the role of key residues.
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 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 c₁ 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.
Center for Biophysics & Computational Biology, University of Illinois at Urbana-Champaign, USA.
Oleksandr
O
Kokhan
Colin A
CA
Wraight
Emad
E
Tajkhorshid
D002462:Cell Membrane / Q000378:metabolism; D018360:Crystallography, X-Ray; D045304:Cytochromes c / Q000737:chemistry* / Q000378:metabolism*; D003575:Cytochromes c1 / Q000737:chemistry* / Q000378:metabolism*; D014450:Electron Transport Complex III / Q000737:chemistry* / Q000378:metabolism*; D006860:Hydrogen Bonding; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D012492:Salts / Q000737:chemistry
D012492:Salts; D045304:Cytochromes c; D003575:Cytochromes c1; D014450:Electron Transport Complex III