Charge Transfer between [4Fe4S] Proteins and DNA Is Unidirectional: Implications for Biomolecular Signaling.


Journal Article

Recent experiments suggest that DNA-mediated charge transport might enable signaling between the [4Fe4S] clusters in the C-terminal domains of human DNA primase and polymerase α, as well as the signaling between other replication and repair high-potential [4Fe4S] proteins. Our theoretical study demonstrates that the redox signaling cannot be accomplished exclusively by DNA-mediated charge transport because part of the charge transfer chain has an unfavorable free energy profile. We show that hole or excess electron transfer between a [4Fe4S] cluster and a nucleic acid duplex through a protein medium can occur within microseconds in one direction, while it is kinetically hindered in the opposite direction. We present a set of signaling mechanisms that may occur with the assistance of oxidants or reductants, using the allowed charge transfer processes. These mechanisms would enable the coordinated action of [4Fe4S] proteins on DNA, engaging the [4Fe4S] oxidation state dependence of the protein-DNA binding affinity.

Full Text

Duke Authors

Cited Authors

  • Teo, RD; Rousseau, BJG; Smithwick, ER; Di Felice, R; Beratan, DN; Migliore, A

Published Date

  • January 2019

Published In

Volume / Issue

  • 5 / 1

Start / End Page

  • 122 - 137

PubMed ID

  • 30714018

Pubmed Central ID

  • 30714018

Electronic International Standard Serial Number (EISSN)

  • 2451-9294

International Standard Serial Number (ISSN)

  • 2451-9294

Digital Object Identifier (DOI)

  • 10.1016/j.chempr.2018.09.026


  • eng