Nucleic acid tertiary structure

Nucleic acid tertiary structure is the three-dimensional shape of a nucleic acid polymer. RNA and DNA molecules are capable of diverse functions ranging from molecular recognition to catalysis. Such functions require a precise three-dimensional structure. While such structures are diverse and seemingly complex, they are composed of recurring, easily recognizable tertiary structural motifs that serve as molecular building blocks. Some of the most common motifs for RNA and DNA tertiary structure are described below, but this information is based on a limited number of solved structures. Many more tertiary structural motifs will be revealed as new RNA and DNA molecules are structurally characterized.

The double helix is the dominant tertiary structure for biological DNA, and is also a possible structure for RNA. Three DNA conformations are believed to be found in nature, A-DNA, B-DNA, and Z-DNA. The "B" form described by James D. Watson and Francis Crick is believed to predominate in cells. James D. Watson and Francis Crick described this structure as a double helix with a radius of 10 Å and pitch of 34 Å, making one complete turn about its axis every 10 bp of sequence. The double helix makes one complete turn about its axis every 10.4–10.5 base pairs in solution. This frequency of twist (known as the helical pitch) depends largely on stacking forces that each base exerts on its neighbours in the chain. Double-helical RNA adopts a conformation similar to the A-form structure.

Other conformations are possible; in fact, only the letters F, Q, U, V, and Y are now available to describe any new DNA structure that may appear in the future. However, most of these forms have been created synthetically and have not been observed in naturally occurring biological systems.

The minor groove triplex is a ubiquitous RNA structural motif. Because interactions with the minor groove are often mediated by the 2'-OH of the ribose sugar, this RNA motif looks very different from its DNA equivalent. The most common example of a minor groove triple is the A-minor motif, or the insertion of adenosine bases into the minor groove (see above). However, this motif is not restricted to adenosines, as other nucleobases have also been observed to interact with the RNA minor groove.

The minor groove presents a near-perfect complement for an inserted base. This allows for optimal van der Waals contacts, extensive hydrogen bonding and hydrophobic surface burial, and creates a highly energetically favorable interaction. Because minor groove triples are capable of stably packing a free loop and helix, they are key elements in the structure of large ribonucleotides, including the group I intron, the group II intron, and the ribosome.

Although the major groove of standard A-form RNA is fairly narrow and therefore less available for triplex interaction than the minor groove, major groove triplex interactions can be observed in several RNA structures. These structures consist of several combinations of base pair and Hoogsteen interactions. For example, the GGC triplex (GGC amino(N-2)-N-7, imino-carbonyl, carbonyl-amino(N-4); Watson-Crick) observed in the 50S ribosome, composed of a Watson-Crick type G-C pair and an incoming G which forms a pseudo-Hoogsteen network of hydrogen bonding interactions between both bases involved in the canonical pairing. Other notable examples of major groove triplexes include (i) the catalytic core of the group II intron shown in the figure at left (ii) a catalytically essential triple helix observed in human telomerase RNA (iii) the SAM-II riboswitch and (iv) the element for nuclear expression (ENE), which acts as an RNA stabilization element through triple helix formation with the poly(A) tail.

Triple-stranded DNA is also possible from Hoogsteen or reversed Hoogsteen hydrogen bonds in the major groove of B-form DNA.

Besides double helices and the above-mentioned triplexes, RNA and DNA can both also form quadruple helices. There are diverse structures of RNA base quadruplexes. Four consecutive guanine residues can form a quadruplex in RNA by Hoogsteen hydrogen bonds to form a “Hoogsteen ring” (See Figure). G-C and A-U pairs can also form base quadruplex with a combination of Watson-Crick pairing and noncanonical pairing in the minor groove.