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Protein-protein interfaces from cytochrome c oxidase I evolve faster than nonbinding surfaces, yet negative selection is the driving force.

Aledo JC, Valverde H, Ruíz-Camacho M, Morilla I, López FD - Genome Biol Evol (2014)

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.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Biología Molecular y Bioquímica, Facultad de Ciencias, Universidad de Málaga, Spain caledo@uma.es.

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Uneven selective pressure on different COX I subset of residues. Using fixed-sites codon-substitution models, the selective pressure of the indicated subsets of residues was estimated. As it can be observed, residues from the COX I Exposed Noncontact group that do not take part in protein–protein interfaces are subjected to a remarkable selective pressure. The standard errors, which are omitted from the figure, are without exception below 2.5%.
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evu240-F5: Uneven selective pressure on different COX I subset of residues. Using fixed-sites codon-substitution models, the selective pressure of the indicated subsets of residues was estimated. As it can be observed, residues from the COX I Exposed Noncontact group that do not take part in protein–protein interfaces are subjected to a remarkable selective pressure. The standard errors, which are omitted from the figure, are without exception below 2.5%.

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.—


Protein-protein interfaces from cytochrome c oxidase I evolve faster than nonbinding surfaces, yet negative selection is the driving force.

Aledo JC, Valverde H, Ruíz-Camacho M, Morilla I, López FD - Genome Biol Evol (2014)

Uneven selective pressure on different COX I subset of residues. Using fixed-sites codon-substitution models, the selective pressure of the indicated subsets of residues was estimated. As it can be observed, residues from the COX I Exposed Noncontact group that do not take part in protein–protein interfaces are subjected to a remarkable selective pressure. The standard errors, which are omitted from the figure, are without exception below 2.5%.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4255772&req=5

evu240-F5: Uneven selective pressure on different COX I subset of residues. Using fixed-sites codon-substitution models, the selective pressure of the indicated subsets of residues was estimated. As it can be observed, residues from the COX I Exposed Noncontact group that do not take part in protein–protein interfaces are subjected to a remarkable selective pressure. The standard errors, which are omitted from the figure, are without exception below 2.5%.
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.—

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.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Biología Molecular y Bioquímica, Facultad de Ciencias, Universidad de Málaga, Spain caledo@uma.es.

Show MeSH