Naslov
Stabilizing interactions in a long-loop G-quadruplex formed within promoters of Plasmodium falciparum B var genes

Autori
Juribašić Kulcsar, Marina ; Gabelica, Valérie ; Plavec, Janez

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
ANNA2016, Advances in Noncanonical Nucleic Acids / - , 2016

Skup
ANNA2016, Advances in Noncanonical Nucleic Acids

Mjesto i datum
Ljubljana, Slovenija, 18.05.2016. - 20.05.2016

Vrsta sudjelovanja
Predavanje

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
G-quadruplex, structure, DNA, NMR spectroscopy, Plasmodium falciparum

Sažetak
G-quadruplexes formed by guanine-rich nucleic acid sequences influence many key biological functions thus being in the spotlight of chemical and biological investigations, pharmaceutics and nanotechnology. Structures consist of Hoogsteen hydrogen-bonded guanines forming G-quartets that are connected by loops whose prolongation usually reduces thermal stability of the structure. We report NMR high-resolution solution-state structure of an intramolecular DNA G-quadruplex with unprecedented ten-nucleotides (10-nt) long loop which breaks the traditional loop length dogma of maximum seven nucleotides expected for maintaining a stable structure. UpsB-Q-1, a 34-nt long oligonucleotide, d[CAG3T2A2G3TATA2CT3AG4T2AG3T2], found within promoters of Plasmodium falciparum var genes, that play a key role in malaria pathogenesis and immune evasion, folds under near-physiological conditions into a structurally unique [3+1]-hybrid structure (Figure 1). Apart from twelve guanine residues in G-quartets, ten additional sites in loop regions are engaged in interactions on both quadruplex-loop interfaces and constitute characteristic 10-nt hairpin and sheared GTTA edqewise loop essential for maintaining a stable fold. The structure displays distinct loop interactions that evidence how stabilization of extra-long loops leads to biologically-relevant structures that are stable at physiological conditions and could be exploited as potential drug targets.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

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