Duplex-quadruplex motifs in a peculiar structural organization cooperatively contribute to thrombin binding of a DNA aptamer

Acta Crystallogr D Biol Crystallogr. 2013 Dec;69(Pt 12):2403-11. doi: 10.1107/S0907444913022269. Epub 2013 Nov 19.

Abstract

Potent second-generation thrombin aptamers adopt a duplex-quadruplex bimodular folding and recognize thrombin exosite II with very high affinity and specificity. A sound model of these oligonucleotides, either free or in complex with thrombin, is not yet available. Here, a structural study of one of these aptamers, HD22-27mer, is presented. The crystal structure of this aptamer in complex with thrombin displays a novel architecture in which the helical stem is enchained to a pseudo-G-quadruplex. The results also underline the role of the residues that join the duplex and quadruplex motifs and control their recruitment in thrombin binding.

Keywords: aptamers; duplex–quadruplex motifs; thrombin.

MeSH terms

  • Aptamers, Nucleotide / chemistry
  • Aptamers, Nucleotide / metabolism*
  • Base Sequence
  • Crystallography, X-Ray
  • Humans
  • Models, Molecular
  • Nucleic Acid Conformation
  • Protein Binding
  • Thrombin / chemistry
  • Thrombin / metabolism*

Substances

  • Aptamers, Nucleotide
  • thrombin aptamer
  • Thrombin

Associated data

  • PDB/4I7Y