Energetic Basis of AGCGA‐Rich DNA Folding into a Tetrahelical Structure. (25th January 2019)

• Record Type: Journal Article
• Authors: Hadži, San; Kocman, Vojč; Oblak, Domen; Plavec, Janez; Lah, Jurij
• Is Part Of: Angewandte Chemie. Volume 131:Number 8(2019)
• Page Start: 2409
• Page End: 2413
• Publication Date: 2019-01-25
• Subjects: AGCGA-Wiederholungseinheit -- DNA -- DNA-Strukturen -- Dynamische Differenzkalorimetrie -- Quadruplexe; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.201813502
• Languages: English
• ISSNs: 0044-8249

Abstract

Abstract: It was recently discovered that, besides well‐known G‐quadruplexes and i‐motifs, DNA may adopt another type of noncanonical structure called AGCGA‐quadruplexes. Here, the folding of the VK2 fragment from the regulatory region of the PLEKHG3 gene is studied and, for the first time, the energetic contributions that stabilize this unique fold are described. Similarly to the B‐DNA, it is stabilized by hydrophobic desolvation and, in contrast to G‐quadruplexes, also by specific binding of water molecules. Compared to B‐DNA, VK2 folding is enthalpically less favorable due to poorer base‐stacking interactions, resulting in substantial conformational flexibility. This entropically favorable conformational "breathing" stabilizes the AGCGA‐quadruplexes. In conclusion, AGCGA‐quadruplexes have a distinguishing thermodynamic fingerprint and the corresponding driving forces enabling their folding are consistent with the observed structural features. Abstract : Die Faltungsenergetik einer neuartigen Klasse nichtkanonischer DNA‐Strukturen, AGCGA‐Quadruplex genannt, wird beschrieben. Diese Strukturen haben einen anderen thermodynamischen Fingerabdruck als B‐DNA und G‐Quadruplexe. Basenstapelung, hydrophobe Desolvatisierung, konformative Flexibilität und spezifische Bindung von Wassermolekülen sind wesentliche energetische Beiträge, welche die AGCGA‐Quadruplex‐Faltung antreiben.