What is the significance for maintaining the evolutionarily conserved conformation flexibility in the RNA-binding ring of the archaeal exosome and PNPase?
The observed conformational heterogeneity agrees perfectly with the function of the RNA-binding ring of the exosome to accommodate diverse RNA substrates.
Since increased conformational flexibility was also observed in the RNA-binding ring of the related bacterial PNPase, we speculate that this may reflect an evolutionarily conserved mechanism to accommodate diverse RNA substrates for degradation.
Interestingly, it was found that significantly higher conformational flexibility and thermal motions are present in the RNA-binding ring of the crystal structures of the exosome-related PNPases from mesophilic bacteria, Escherichia coli [29] and Streptomyces antibioticus [25].
Since conformational flexibility was also observed in the RNA-binding ring of the bacterial PNPase [25], [29], we propose that the conformational dynamics may be harnessed by the archaeal exosome, and perhaps by all exosome family members, to accommodate the binding of various RNA substrates and to disrupt their structures.
But over the last few decades, many environmentalists and religious seekers have begun finding their way back to the notion that nature may be, after all, the binding ring of life, just as Cole imagined.
We demonstrate that deletions designed to constrict the DNA-binding ring of Ku80 disrupt nonhomologous end-joining (NHEJ), telomeric gene silencing, and telomere length maintenance, suggesting that these functions require Ku's DNA end-binding activity.
The three Rrp4 subunits (designated Chains C, F, and I in our structure, respectively) in the RNA-binding ring of our structure, however, deviate significantly from their three-fold symmetric positions as reported previously (Fig. 2 [30]).
RNA substrate likely gains access to the "processing chamber" from the side of the RNA-binding ring through a narrow pore at the neck region, which only allows the passage of a single-stranded (ss) RNA [31], [32], [33]}.
The RNA-binding ring (occupying 23% of the entire PNPase) in E. coli PNPase is so flexible that it could not be successfully traced from the electron density map [29].
These two residues had previously been identified to be important for substrate binding (accommodating the hydrophobic phenyl ring of the substrate) and stereoselectivity of OYE enzymes.
