Faculty, Staff and Student Publications

Publication Date

11-1-2024

Journal

FEBS Letters

DOI

10.1002/1873-3468.15011

PMID

39245885

PMCID

PMC11560498

PubMedCentral® Posted Date

11-1-2025

PubMedCentral® Full Text Version

Author MSS

Abstract

Conjugative dissemination of mobile genetic elements (MGEs) among bacteria is initiated by assembly of the relaxosome at the MGE’s origin-of-transfer (oriT) sequence. A critical but poorly defined step of relaxosome assembly involves recruitment of the catalytic relaxase to its DNA strand-specific nicking site within oriT. Here, we present evidence by AlphaFold modeling, affinity pulldowns, and in vivo site-directed photocrosslinking that the TraK Ribbon-Helix-Helix DNA-binding protein recruits TraI to oriT through a dynamic interaction in which TraI’s C-terminal unstructured domain (TraICTD) wraps around TraK’s C-proximal tetramerization domain. Upon relaxosome assembly, conformational changes disrupt this contact, and TraICTD instead self-associates as a prerequisite for relaxase catalytic functions or substrate engagement with the transfer channel. These findings delineate key early-stage processing reactions required for conjugative dissemination of a model MGE.

Keywords

Escherichia coli Proteins, Conjugation, Genetic, Escherichia coli, Plasmids, DNA-Binding Proteins, Models, Molecular, Protein Binding, DNA Helicases, Conjugation, horizontal DNA transfer, mobile genetic elements, antibiotic resistance, type IV secretion, AlphaFold, photocrosslinking, Ribbon-Helix-Helix, relaxase

Published Open-Access

yes

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