Allosterically tunable, DNA-based switches triggered by heavy metals

J Am Chem Soc. 2013 Sep 11;135(36):13238-41. doi: 10.1021/ja404653q. Epub 2013 Aug 28.

Abstract

Here we demonstrate the rational design of allosterically controllable, metal-ion-triggered molecular switches. Specifically, we designed DNA sequences that adopt two low energy conformations, one of which does not bind to the target ion and the other of which contains mismatch sites serving as specific recognition elements for mercury(II) or silver(I) ions. Both switches contain multiple metal binding sites and thus exhibit homotropic allosteric (cooperative) responses. As heterotropic allosteric effectors we employ single-stranded DNA sequences that either stabilize or destabilize the nonbinding state, enabling dynamic range tuning over several orders of magnitude. The ability to rationally introduce these effects into target-responsive switches could be of value in improving the functionality of DNA-based nanomachines.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allosteric Regulation / drug effects
  • Amino Acid Sequence
  • Binding Sites / drug effects
  • DNA, Single-Stranded / chemistry*
  • DNA, Single-Stranded / drug effects
  • Metals, Heavy / chemistry*
  • Metals, Heavy / pharmacology

Substances

  • DNA, Single-Stranded
  • Metals, Heavy