A research team at the University of Tokyo has discovered a mechanism for pH-dependent regulation of binding affinity in thioester domains (TEDs), which are found in bacterial adhesion proteins across diverse lineages.
TEDs form covalent bonds with their targets, providing a strong molecular attachment. Yet strong does not necessarily mean permanent. Using biolayer interferometry to track binding and dissociation in real time, the researchers showed that the TED from the SfbI adhesion protein of group A Streptococcus pyogenes releases the host protein fibrinogen rapidly when conditions become mildly acidic.
Biochemical experiments and thermodynamic analysis indicate that this response is rooted in the reaction that forms the covalent bond: acidification favors the reverse reaction, allowing the covalent attachment to come undone. Evidence from the TED of CpTIE in the distantly related bacterium Clostridium perfringens supports the idea that pH sensitivity is intrinsic to the chemistry shared by this protein family, although its observable effects may vary among TEDs.
Bacteria commonly respond to environmental changes by altering gene expression. This study points to an additional route: adhesion proteins can respond directly through their own chemistry, without waiting for changes in protein production. The findings suggest that TEDs may function as pH-responsive adhesion modules rather than permanent anchors, offering a new perspective on how bacteria interact with their surroundings and hosts.
pH-Responsive Adhesion Mediated by Thioester Domains of Bacterial Adhesins
Papers
Journal: Science Advances
Title: Chemically encoded pH-tunable covalent adhesion by a bacterial thioester domain
Authors: Yuki Tokunaga, Ryo Matsunaga*, Hiroko Kozuka-Hata, Masaaki Oyama, Kouhei Tsumoto*