Protein-protein interfaces from cytochrome c oxidase I evolve faster than nonbinding surfaces, yet negative selection is the driving force.
Bottom Line: Herein, using evolutionary data in combination with structural information of COX, we show that failing to discern the effects of interaction from other structural and functional effects can lead to deceptive conclusions such as the "optimizing hypothesis." Once spurious factors have been accounted for, data analysis shows that mtDNA-encoded residues engaged in contacts are, in general, more constrained than their noncontact counterparts.This differential behavior cannot be explained on the basis of predicted thermodynamic stability, as interactions between mtDNA-encoded subunits contribute more weakly to the complex stability than those interactions between subunits encoded by different genomes.Therefore, the higher conservation observed among mtDNA-encoded residues involved in intragenome interactions is likely due to factors other than structural stability.
Affiliation: Departamento de Biología Molecular y Bioquímica, Facultad de Ciencias, Universidad de Málaga, Spain email@example.com.Show MeSH
Mentions: Using the sequence from Bos taurus as reference and the crystal structure of bovine COX (Protein Data Bank, PDB, 2OCC), each codon position from the above described alignments was sorted into different subsets according to the algorithm sketched in figure 1. Briefly, the data set corresponding to all the codons from the alignment of a given COX subunit (for instance, chain A, corresponding to COX I, which is a mtDNA-encoded subunit) was initially divided into two subsets: “Contact” and “Noncontact,” depending on whether the encoded amino acid from chain A is or not closer than 4 Å to a residue from any polypeptide other than chain A, respectively. The distance between two amino acids is given by the minimal distance between all pairs of heavy atoms from the two residues. Interacting positions were defined as being less than 4 Å apart because this is the upper limit for weak interactions (Martin et al. 1997). Afterwards, the Contact set was, in turn, split into two subsets: Intergenomic Contact (“Mt–nu Contact,” in the example) and Intragenomic Contact (“Mt–mt Contact,” in the example). The criterion to assign a given codon into the former subset was that the interacting residues should have been encoded by different genomes, otherwise the codon was allocated into the latter subset. On the other hand, the Noncontact set was split up into two subsets: “Exposed Noncontact” and “Buried Noncontact,” on the basis of solvent accessible surface areas of the considered residue (Aledo et al. 2012).Fig. 1.—
Affiliation: Departamento de Biología Molecular y Bioquímica, Facultad de Ciencias, Universidad de Málaga, Spain firstname.lastname@example.org.