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A bacterial thioester domain functions as a pH-responsive covalent adhesion module

Tokunaga, Y.; Matsunaga, R.; Oyama, M.; Kozuka-Hata, H.; Tsumoto, K.

2026-02-07 biochemistry
10.64898/2026.02.05.703941 bioRxiv
Show 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 revealed that this pH-responsiveness arises from the intrinsic properties of the thioester bond within the TED. Similar pH-dependent behavior was observed in phylogenetically distinct TEDs, suggesting that pH-responsive adhesion is a conserved feature of the TED family across Gram-positive bacteria.

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