The Transition from a Neutral-pH Double Helix to a Low-pH Triple Helix Induces a Conformational Switch in the CCCG Tetraloop Closing a Watson-Crick Stem

Abstract

The CCCG-loop in a DNA fragment, which is capable of forming an Structure, Design, and intramolecular triple helix as well as a hairpin structure, was investigated Synthesis, Laboratory of by NMR and molecular modeling studies. We used molecular modeling to lay the foundations for understanding 2300 RA Leiden the observed conformational switch. A lower amount of strain, related to The Netherlands the short C1'-C1' of the base-pair, and protonation effects of the structure comprising the Hoogsteen base-pair turn out to outweigh the effects of a more stable base-pair, improved stacking and more favorable interactions in the minor groove of the structure comprising the Watson-Crick C·G base-pair. The models also provide an explanation for the general preference of loops meeting the consensus sequence -d(CYNG)-to fold into a type II conformation, i.e. with the base of second loop residue turned into the minor groove.

Theoretical analysis of noncanonical base pairing interactions in RNA molecules

“…As shown in fi gure 6, our structure could be shown to be explainable only in terms of a G:G(+) base pairing. As explained in the fi gure, it seems possible that the trans G:G H:W confi guration in conjunction with our trans G:G(+) H:S pair could act like a pH dependent conformational switch as in the case of the cis G:C W:W to cis G:C H:W switch discussed earlier (van Dongen et al 1996). It is also reasonable to suppose that the trans G:G(+) H:S confi guration which we have shown in fi gure 6 is the proper confi guration and the example we have chosen for computation is an intermediate for the switching process.…”

“…Even when they do so, they would be constrained such that they cannot easily fl ip into forming canonical pairs, unless of course that is what is expected of them. For example, it has been reported that the transition from a neutral-pH double helix to a low-pH triple helix, involving a canonical G:C pair fl ipping to a hoogsteen C(+):G pair, induces a conformational switch in the CCCG tetraloop closing Watson-Crick stem (van Dongen et al 1996). With such specifi c functional and environmental constraints, it is not surprising that cis G: C(+) H:W base pair (system 26) was found to occur only four times in our database of 145 RNA structures (Das et al 2006), though the computed interaction energy of the base pairing was quite good .…”

New insights into the genetic instability in CCTG repeats

“…2B) when compared to those of random coils (À3.87 to À4.15 ppm) [23]. These unusual 31 P chemical shifts show the special backbone features of type II loop [16,24]. In addition, the unusually downfield H1 0 signals of C2 (6.45 ppm) and C6 (6.46 ppm), and the unusually upfield H1 0 signals of T3 (5.43 ppm) and T7 (5.64 ppm) (Fig.…”

Unusual structures of TTTA repeats in icaC gene of Staphylococcus aureus

“…In addition to the two hydrogen bonds, the base stacked on top of the closing Hoogsteen base pair also contributes to the stability of the mini-loop [20]. Owing to the shorter interstrand C1 0 -C1 0 distance, the stacking interactions are more effective than those involving a closing Watson-Crick base pair [19,21]. In (TTTA) 3 , the base orientation of A8 also possesses the syn feature as evidenced by the similar NOE intensities of H8-H1 0 and H8-H2 0 /H2 00 (Fig.…”