(Redirected from Noncanonical base pair)
Base pairs (BP) are the building blocks of stucture in Eterna. They form when complementary bases associate with one another. Three pairs are possible in Eterna:
Base pairs with unusual geometries and the interactions between mismatched bases are not explicitly depicted in Eterna.
Base pairs can be considered the "glue" that holds together a folded RNA. Breaking a base pair that has already formed requires the addition of energy to the RNA.
Base pairing results from a combination of hydrogen bonding and hydrophobic stacking interactions. These interactions are only favorable with certain combinations of bases in specific orientations.
Base pairs vary in strength. The GC pair is stronger than AU or GU pairs due to the presence of an additional hydrogen bond and stronger stacking interactions. Additionally, the energy of a base pair can be altered by exchanging the positions of two paired bases. A GC pair with guanine in the 5' direction of cytosine will not make the same energy contribution as a CG pair with guanine in the 3' direction of cytosine.
Watson-Crick Base Pairs
The AU pair and GC pair are known as Watson-Crick base pairs. These are the most commonly encountered type of base pairs in double-stranded regions of RNA. The geometry of these two pairs in double-stranded RNA is nearly identical.
Watson-Crick Pairs in Eterna
The GC pair is stronger than the AU pair by up to 2 kcal/mol, and it is more stabilizing when it appears as a closing base pair.
Wobble pairs are non-Watson-Crick pairs involving bases at the final "wobble" position of the codon-anticodon pair. The ability to form these pairs allows a single tRNA to recognize multiple codons in mRNA. One of the first wobble pairs to be recognized is the GU pair. Other common pairings that occur in this position involve the nonstandard purine base inosine and cytosine, adenine, or uracil. The GU pair is not restricted to the wobble position in the codon/anticodon pair. It is common in natural RNAs, often appearing in regions of the molecule where protein-RNA interactions occur. The geometry of the GU pair differs from that of the AU and GC pairs. The distortion of the double-helix disrupts stacking interactions in the 5' direction of guanine. Closing GU pairs in nature are usually oriented in a way that places the first unpaired base of the loop 5' of guanine.
Wobble Pairs in Eterna
In Eterna, only the GU wobble pair is represented. When flanked by AU or GC pairs, the GU pair behaves similar to AU pair. When flanked by other GU pairs, the GU pair is very weak or destabilizing.
Other Noncanonical Base Pairs
Provided the right environment and orientation, any combination of the four common RNA bases can form hydrogen bonds. Additionally, three or more bases may interact to form triplex and quadruplex structures. These noncanonical base pairs can be seen in the atomic-level structures of many RNAs, but energy parameters for these pairs do not exist and they cannot be predicted from sequence.
Noncanonical Base Pairs in Eterna
Noncanonical pairs are not displayed in Eterna; however, the energy bonus from boosting reflects the formation of certain noncanonical pairs in loops.
Base Pairs at the Atomic Level
Further Information: Jena Library
When atomic-level structural information is available, base pairs can be further classified according to the orientation of the interacting nucleotides. Base pairs are frequently described according to the type of pair, the interacting base edges, and orientation of the glycosidic bond.
In Watson-Crick base pairs, hydrogen bonding between bases involves a specific region of each nucleotide. Nucleotides contain many hydrogen bond donors and acceptors outside of this region that can also participate in base-pairing. Hydrogen bonding between two bases can involve any combination of three general regions, or edges.
Following video illustratres how different edges of Guanine are bonded when involved in either a canonical GC pair, or a so-called sheared G.A
Glycosidic Bond Orientation
A glycosidic bond joins the sugar, ribose, and the base in a nucleotide. The glycosidic bonds of the two bases in a base pair can be oriented in the same (cis) or opposing (trans) directions.
Tautomerization alters the arrangement of hydrogen bond donors and acceptors in a base and can allow the formation of additional hydrogen bonds.
In certain base pairs, particularly the U-U pair, pairing occurs through a water molecule located between the two bases. Both bases form hydrogen bonds to the same water molecule.
Certain noncanonical pairs have common names. For example, a "sheared GA pair" involves hydrogen bonding between the Hoogsteen and Sugar edges of guanine and adenine with a trans- orientation of the glycosidic bond.