Structural modelling and functional analysis support lipid binding by the dimeric E. coli DedA protein YqjA
- 1University of Kent
Abstract
Maintenance of membrane homeostasis is essential for bacterial viability, yet the molecular functions of many membrane proteins involved in this process remain poorly understood. The widely distributed DedA superfamily of integral membrane proteins has been implicated in membrane homeostasis, with deletion of DedA genes resulting in sensitivities to temperature, pH and a range of antimicrobial compounds. Several bacterial DedA proteins have been linked to lipid transport, providing a potential connection between function and phenotype. However, a lack of direct functional and structural data means that the precise role of DedA proteins in bacterial membrane homeostasis remains unclear. Here, using analytical ultracentrifugation (AUC), we show that the Escherichia coli DedA protein YqjA exists predominantly as a dimer and, by combining structural modelling with site-specific cysteine crosslinking, we have identified the most likely dimer interface. Modelling of dimeric YqjA in the presence of lipids predicts an interfacial lipid-binding site located in close proximity to several conserved, functionally important residues. Consistent with lipid binding, addition of lipid substantially increased the thermal stability of YqjA. Furthermore, mutation of residues associated with the predicted binding site impaired YqjA function. Together, these findings provide new structural and functional insights into the DedA family and support a role for lipid binding in the activity of YqjA.
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BibTeX
@misc{paige2026structural,
title = {{Structural modelling and functional analysis support lipid binding by the dimeric E. coli DedA protein YqjA}},
author = {T. J. Paige and J. Chen and A. Le Roy and C. D. D. Sampson and B. F. Cooper and M. Batson and H. L. Scarsbrook and L. R. Forrest and G. L. Isom and C. Mas and V. Leone and C. Mulligan},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.20.752871},
url = {https://www.biorxiv.org/content/10.64898/2026.09.20.752871v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Structural modelling and functional analysis support lipid binding by the dimeric E. coli DedA protein YqjA
AU - T. J. Paige
AU - J. Chen
AU - A. Le Roy
AU - C. D. D. Sampson
AU - B. F. Cooper
AU - M. Batson
AU - H. L. Scarsbrook
AU - L. R. Forrest
AU - G. L. Isom
AU - C. Mas
AU - V. Leone
AU - C. Mulligan
PY - 2026
DA - 2026/09/20
PB - bioRxiv
DO - 10.64898/2026.09.20.752871
UR - https://www.biorxiv.org/content/10.64898/2026.09.20.752871v1
AB - Maintenance of membrane homeostasis is essential for bacterial viability, yet the molecular functions of many membrane proteins involved in this process remain poorly understood. The widely distributed DedA superfamily of integral membrane proteins has been implicated in membrane homeostasis, with deletion of DedA genes resulting in sensitivities to temperature, pH and a range of antimicrobial compounds. Several bacterial DedA proteins have been linked to lipid transport, providing a potential connection between function and phenotype. However, a lack of direct functional and structural data means that the precise role of DedA proteins in bacterial membrane homeostasis remains unclear. Here, using analytical ultracentrifugation (AUC), we show that the Escherichia coli DedA protein YqjA exists predominantly as a dimer and, by combining structural modelling with site-specific cysteine crosslinking, we have identified the most likely dimer interface. Modelling of dimeric YqjA in the presence of lipids predicts an interfacial lipid-binding site located in close proximity to several conserved, functionally important residues. Consistent with lipid binding, addition of lipid substantially increased the thermal stability of YqjA. Furthermore, mutation of residues associated with the predicted binding site impaired YqjA function. Together, these findings provide new structural and functional insights into the DedA family and support a role for lipid binding in the activity of YqjA.
ER -