Chemically encoded pH-tunable covalent adhesion by a bacterial thioester domain
- 1Department of Bioengineering, School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
- 2The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
- 3Department of Chemistry and Biotechnology, School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
Abstract
Thioester domains (TEDs) represent a family of bacterial adhesin domains that mediate covalent anchoring to target ligands via an intramolecular thioester bond. Although the broad distribution of TEDs among Gram-positive bacteria suggests a critical functional role, the biological significance of this covalent mechanism remains unclear. In this study, we demonstrated that TED-mediated covalent anchoring is reversible and that its equilibrium is regulated by pH. Specifically, SfbI-TED from group A Streptococcus binds tightly to fibrinogen at physiological pH, whereas mild acidification to pH 6.0 induces rapid dissociation of the complex. Thermodynamic analyses indicated that this pH responsiveness is largely dictated by the intrinsic pH sensitivity of the thioester-mediated acyl transfer reaction conserved within TEDs, rather than by surface residues specific to individual TEDs. Similar pH-dependent behavior was observed in phylogenetically distinct TEDs, suggesting that pH-responsive adhesion is likely to be a broadly shared feature of TED-containing adhesins across Gram-positive bacteria.
Related
- A thioester-thiol exchange reaction in Salmonella Invasion acyl carrier protein transfers the 4PP-bound acyl chain to a distal cysteine
- Peptide nitrile ligation enables thioester-free chemical protein synthesis
- Development of oligo-thioester precursors for native chemical ligation of oligo-protein conjugates.
- Single cell RNA-seq analysis identifies junctional adhesion molecule two positive endothelial cells aggravate osteoarthritis by mediating vascular permeability and macrophage adhesion
- Chemically Induced Proximity in Biological Modulation.
BibTeX
@article{tokunaga2026chemically,
title = {{Chemically encoded pH-tunable covalent adhesion by a bacterial thioester domain}},
author = {Yuki Tokunaga and Ryo Matsunaga and Hiroko Kozuka-Hata and Masaaki Oyama and Kouhei Tsumoto},
journal = {Science Advances},
year = {2026},
month = oct,
doi = {10.1126/sciadv.aeg7646},
url = {https://www.science.org/doi/10.1126/sciadv.aeg7646},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Chemically encoded pH-tunable covalent adhesion by a bacterial thioester domain
AU - Yuki Tokunaga
AU - Ryo Matsunaga
AU - Hiroko Kozuka-Hata
AU - Masaaki Oyama
AU - Kouhei Tsumoto
PY - 2026
DA - 2026/10/21
JO - Science Advances
DO - 10.1126/sciadv.aeg7646
UR - https://www.science.org/doi/10.1126/sciadv.aeg7646
AB - Thioester domains (TEDs) represent a family of bacterial adhesin domains that mediate covalent anchoring to target ligands via an intramolecular thioester bond. Although the broad distribution of TEDs among Gram-positive bacteria suggests a critical functional role, the biological significance of this covalent mechanism remains unclear. In this study, we demonstrated that TED-mediated covalent anchoring is reversible and that its equilibrium is regulated by pH. Specifically, SfbI-TED from group A Streptococcus binds tightly to fibrinogen at physiological pH, whereas mild acidification to pH 6.0 induces rapid dissociation of the complex. Thermodynamic analyses indicated that this pH responsiveness is largely dictated by the intrinsic pH sensitivity of the thioester-mediated acyl transfer reaction conserved within TEDs, rather than by surface residues specific to individual TEDs. Similar pH-dependent behavior was observed in phylogenetically distinct TEDs, suggesting that pH-responsive adhesion is likely to be a broadly shared feature of TED-containing adhesins across Gram-positive bacteria.
SN - 2375-2548
ER -