Working Paper Article Version 1 This version is not peer-reviewed

Towards Understanding of Polymorphism of G-Rich Region of Human Papillomavirus Type 52

Version 1 : Received: 16 March 2019 / Approved: 18 March 2019 / Online: 18 March 2019 (10:00:21 CET)

A peer-reviewed article of this Preprint also exists.

Marušič, M.; Plavec, J. Towards Understanding of Polymorphism of the G-rich Region of Human Papillomavirus Type 52. Molecules 2019, 24, 1294. Marušič, M.; Plavec, J. Towards Understanding of Polymorphism of the G-rich Region of Human Papillomavirus Type 52. Molecules 2019, 24, 1294.

Journal reference: Molecules 2019, 24, 1294
DOI: 10.3390/molecules24071294

Abstract

The potential to affect gene expression via G-quadruplex stabilization has been extended to all domains of life, including viruses. Here, we investigate the polymorphism and structures of G-quadruplexes of the human papillomavirus type 52 with UV, CD and NMR spectroscopy and gel electrophoresis. We show that oligonucleotide with five G-tracts folds into several structures and that naturally occurring single nucleotide polymorphisms (SNPs) have profound effects on the structural polymorphism in the context of G-quadruplex forming propensity, conformational heterogeneity and folding stability. With help of SNP analysis, we were able to select one of the predominant forms, formed by G-rich sequence d(G3TAG3CAG4ACACAG3T). This oligonucleotide termed HPV52(1-4) adopts a three G-quartet snap back (3+1) type scaffold with four syn guanine residues, two edgewise loops spanning the same groove, a no-residue V loop and a propeller type loop. The first guanine residue is incorporated in the central G-quartet and all four-guanine residues from G4 stretch are included in the three quartet G-quadruplex core. Modification studies identified several structural elements that are important for stabilization of the described G-quadruplex fold. Our results expand set of G-rich targets in viral genomes and address the fundamental questions regarding folding of G-rich sequences.

Subject Areas

G-quadruplex; NMR; folding; DNA; structure; human papillomaviruses

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