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bioRxiv · 10.64898/2026.05.01.722082

Structural Insights into the Coupling Mechanism of Vectorial CO2 Uptake by DAB1

Phillips, N. R.·Oltrogge, L. M.·Remis, J. P.·Savage, D. F.
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Abstract

CO2 transporters enable bacterial carbon-concentrating mechanisms by catalyzing directional hydration of CO2, yet the basis of this vectorial carbonic anhydrase (CA) activity remains an open question. We used cryo-EM to determine the structure of the DAB1 complex from Thermocrinis albus to 2.13 [A], revealing a heterotrimer in which a deeply buried {beta}-CA active site in DabA is structurally coupled to the proton-translocating subunit DabB. Two conformational states define distinct solvent channels for substrate entry and product exit. A suppressor screen identifies mutations that disrupt coupling while retaining CA activity, underlying the importance of conserved residues that link proton translocation to active-site remodeling. These results support a model in which proton-driven conformational changes regulate substrate access to the active site, enabling vectorial CO2 hydration.

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Phillips, N. R., Oltrogge, L. M., Remis, J. P., Savage, D. F.. 2026-05-02. Structural Insights into the Coupling Mechanism of Vectorial CO2 Uptake by DAB1. https://doi.org/10.64898/2026.05.01.722082

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