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Insights into the structural dynamics of the bacteriophage T7 DNA polymerase and its complexes.

ABSTRACT: The T7 DNA polymerase is dependent on the host protein thioredoxin (trx) for its processivity and fidelity. Using all-atom molecular dynamics, we demonstrate the specific interactions between trx and the T7 polymerase, and show that trx docking to its binding domain on the polymerase results in a significant level of stability and exposes a series of basic residues within the domain that interact with the phosphodiester backbone of the DNA template. We also characterize the nature of interactions between the T7 DNA polymerase and its DNA template. We show that the trx-binding domain acts as an intrinsic clamp, constraining the DNA via a two-step hinge motion, and characterize the interactions necessary for this to occur. Together, these insights provide a significantly improved understanding of the interactions responsible for highly processive DNA replication by T7 polymerase.

SUBMITTER: Magill DJ

PROVIDER: S-EPMC5984650 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Insights into the structural dynamics of the bacteriophage T7 DNA polymerase and its complexes.

Magill Damian J DJ McGrath John W JW O'Flaherty Vincent V Quinn John P JP Kulakov Leonid A LA

Journal of molecular modeling 20180601 7

The T7 DNA polymerase is dependent on the host protein thioredoxin (trx) for its processivity and fidelity. Using all-atom molecular dynamics, we demonstrate the specific interactions between trx and the T7 polymerase, and show that trx docking to its binding domain on the polymerase results in a significant level of stability and exposes a series of basic residues within the domain that interact with the phosphodiester backbone of the DNA template. We also characterize the nature of interaction ...[more]

PMID: 29858666

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