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

ABSTRACT: 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 ?, 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.

SUBMITTER: Teo RD 

PROVIDER: S-EPMC6350243 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature