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: As COX I, a polypeptide belonging to the core of the enzymatic complex, interacts with many other subunits from the complex, we reasoned that many residues from its surface may be involved in forming protein–protein interfaces, even when they would not establish interatomic contacts. Therefore, we addressed whether those residues taking part of such interfaces may be responsible for the unusual high degree of conservation described above. To this end, the COX I Exposed Noncontact set (143 residues) was partitioned into “Interface” (68 residues) and “Noninterface” (75 residues) subsets, according to the criterion described in Materials and Methods. Briefly, the residue being sorted was considered as Interface if its surface area was reduced when considered in the complex with respect to the single subunit, otherwise the amino acid was classified as Noninterface. This partition, together with the phylogenetic tree that we had obtained, allowed us to use the program codeml from the PAML package to assess the selective pressure suffered by the different residue categories. The results of such analyses were clear and intriguing (fig. 5). Those solvent-exposed residues from COX I that are neither engaged in intersubunit contacts nor involved in protein interfaces suffer a surprisingly high selective pressure, as judged by a low ω value comparable with that estimated for buried residues, but significantly lower (P < 0.05) than the ω value found for the Interface group (fig. 5). In contrast, those Exposed Noncontact residues from COX I that were involved in protein–protein interfaces showed a much higher ω value, similar to that obtained for contact residues.Fig. 5.—
Affiliation: Departamento de Biología Molecular y Bioquímica, Facultad de Ciencias, Universidad de Málaga, Spain firstname.lastname@example.org.