Limits...
Recognition of Watson-Crick base pairs: constraints and limits due to geometric selection and tautomerism.

Westhof E, Yusupov M, Yusupova G - F1000Prime Rep (2014)

Bottom Line: The natural bases of nucleic acids have a strong preference for one tautomer form, guaranteeing fidelity in their hydrogen bonding potential.However, base pairs observed in recent crystal structures of polymerases and ribosomes are best explained by an alternative base tautomer, leading to the formation of base pairs with Watson-Crick-like geometries.These observations set limits to geometric selection in molecular recognition of complementary Watson-Crick pairs for fidelity in replication and translation processes.

View Article: PubMed Central - PubMed

Affiliation: Architecture et Réactivité de l'ARN, Université de Strasbourg, Institut de Biologie Moléculaire et Cellulaire CNRS, 15 rue René Descartes, F-67084 Strasbourg Cedex France.

ABSTRACT
The natural bases of nucleic acids have a strong preference for one tautomer form, guaranteeing fidelity in their hydrogen bonding potential. However, base pairs observed in recent crystal structures of polymerases and ribosomes are best explained by an alternative base tautomer, leading to the formation of base pairs with Watson-Crick-like geometries. These observations set limits to geometric selection in molecular recognition of complementary Watson-Crick pairs for fidelity in replication and translation processes.

No MeSH data available.


The non-isostericity of the GoU wobble pairsThe wobble base pairs, denoted GoU and UoG, are not isosteric upon reversal. Each third residue of the mRNA is locked by ribosome contacts (indicated by the greyish crescent) and thus only the wobble base 34 in the tRNA anticodon has some mobility. However, from a G34 to a U34, there is a large distance (around 4.0 Å) that the tRNA loop cannot well achieve. The formation of a Watson-Crick configuration is thus favored and this is often accomplished by specific modifications of the U34.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3974571&req=5

fig-003: The non-isostericity of the GoU wobble pairsThe wobble base pairs, denoted GoU and UoG, are not isosteric upon reversal. Each third residue of the mRNA is locked by ribosome contacts (indicated by the greyish crescent) and thus only the wobble base 34 in the tRNA anticodon has some mobility. However, from a G34 to a U34, there is a large distance (around 4.0 Å) that the tRNA loop cannot well achieve. The formation of a Watson-Crick configuration is thus favored and this is often accomplished by specific modifications of the U34.

Mentions: An underappreciated property of wobble pairs is that they are not isosteric upon GoU to UoG reversal. This is particularly relevant if one of the two nucleotides is constrained in an active site, as is the case for nucleotide +3 of the mRNA, which is fixed in the A site of the ribosome to ribosomal nucleotides and protein S12 via a magnesium ion (Figure 3). Thus, for accommodation of any non-standard pair, movements can essentially occur at tRNA residue 34. Because of the tRNA anticodon loop fold, movements towards the minor groove (necessary for a G34oU[+3] pair) are easier than those towards the major groove (required for a U34oG[+3] pair). tRNAs manage, however, by several modifications of residue U34 that stabilize a tautomer change, to form a U34~G(+3) with Watson-Crick-like geometry [70-73]. Reversibly, some U34 modifications, although promoting U34~G(+3) formation, are detrimental to the formation of the standard Watson-Crick U34-A(+3) pair [74]. The importance of U34 modifications for reading G-ending codons has been emphasized several times [75,76]. This is not the only known case where a modification promotes a tautomer form leading to a Watson-Crick-like geometry pair: both 2-agmatinylcytidine or 2-lysylcytidine (lysidine) exist in a tautomer form, guaranteeing pairing with A, so that the isoleucine AUA codon is translated instead of the Methionine AUG codon in bacteria (which is translated with the unmodified CAU anticodon) [77].


Recognition of Watson-Crick base pairs: constraints and limits due to geometric selection and tautomerism.

Westhof E, Yusupov M, Yusupova G - F1000Prime Rep (2014)

The non-isostericity of the GoU wobble pairsThe wobble base pairs, denoted GoU and UoG, are not isosteric upon reversal. Each third residue of the mRNA is locked by ribosome contacts (indicated by the greyish crescent) and thus only the wobble base 34 in the tRNA anticodon has some mobility. However, from a G34 to a U34, there is a large distance (around 4.0 Å) that the tRNA loop cannot well achieve. The formation of a Watson-Crick configuration is thus favored and this is often accomplished by specific modifications of the U34.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3974571&req=5

fig-003: The non-isostericity of the GoU wobble pairsThe wobble base pairs, denoted GoU and UoG, are not isosteric upon reversal. Each third residue of the mRNA is locked by ribosome contacts (indicated by the greyish crescent) and thus only the wobble base 34 in the tRNA anticodon has some mobility. However, from a G34 to a U34, there is a large distance (around 4.0 Å) that the tRNA loop cannot well achieve. The formation of a Watson-Crick configuration is thus favored and this is often accomplished by specific modifications of the U34.
Mentions: An underappreciated property of wobble pairs is that they are not isosteric upon GoU to UoG reversal. This is particularly relevant if one of the two nucleotides is constrained in an active site, as is the case for nucleotide +3 of the mRNA, which is fixed in the A site of the ribosome to ribosomal nucleotides and protein S12 via a magnesium ion (Figure 3). Thus, for accommodation of any non-standard pair, movements can essentially occur at tRNA residue 34. Because of the tRNA anticodon loop fold, movements towards the minor groove (necessary for a G34oU[+3] pair) are easier than those towards the major groove (required for a U34oG[+3] pair). tRNAs manage, however, by several modifications of residue U34 that stabilize a tautomer change, to form a U34~G(+3) with Watson-Crick-like geometry [70-73]. Reversibly, some U34 modifications, although promoting U34~G(+3) formation, are detrimental to the formation of the standard Watson-Crick U34-A(+3) pair [74]. The importance of U34 modifications for reading G-ending codons has been emphasized several times [75,76]. This is not the only known case where a modification promotes a tautomer form leading to a Watson-Crick-like geometry pair: both 2-agmatinylcytidine or 2-lysylcytidine (lysidine) exist in a tautomer form, guaranteeing pairing with A, so that the isoleucine AUA codon is translated instead of the Methionine AUG codon in bacteria (which is translated with the unmodified CAU anticodon) [77].

Bottom Line: The natural bases of nucleic acids have a strong preference for one tautomer form, guaranteeing fidelity in their hydrogen bonding potential.However, base pairs observed in recent crystal structures of polymerases and ribosomes are best explained by an alternative base tautomer, leading to the formation of base pairs with Watson-Crick-like geometries.These observations set limits to geometric selection in molecular recognition of complementary Watson-Crick pairs for fidelity in replication and translation processes.

View Article: PubMed Central - PubMed

Affiliation: Architecture et Réactivité de l'ARN, Université de Strasbourg, Institut de Biologie Moléculaire et Cellulaire CNRS, 15 rue René Descartes, F-67084 Strasbourg Cedex France.

ABSTRACT
The natural bases of nucleic acids have a strong preference for one tautomer form, guaranteeing fidelity in their hydrogen bonding potential. However, base pairs observed in recent crystal structures of polymerases and ribosomes are best explained by an alternative base tautomer, leading to the formation of base pairs with Watson-Crick-like geometries. These observations set limits to geometric selection in molecular recognition of complementary Watson-Crick pairs for fidelity in replication and translation processes.

No MeSH data available.