Structural insights into the coupling mechanism of vectorial CO 2 uptake by DAB1
CO 2 transporters enable bacterial CO 2 -concentrating mechanisms by catalyzing directional hydration of CO 2 , yet the basis of this vectorial carbonic anhydrase (CA) activity remains an open question. We used cryoelectron microscopy to determine the structure of the DAB1 complex from Thermocrinis albus to 2.29 Å, revealing a heterotrimer in which a deeply buried β-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 CO 2 hydration.
Authors
- David F. Savage (ORCID: https://orcid.org/0000-0003-0042-2257)
- Luke M. Oltrogge (ORCID: https://orcid.org/0000-0001-5716-9980)
- Jonathan P. Remis (ORCID: https://orcid.org/0000-0001-8317-4513)
- Naiya R. Phillips (ORCID: https://orcid.org/0000-0003-1836-5182)
Institutions
- Howard Hughes Medical Institute (US)
- Innovative Genomics Institute (US)
Publication Details
- Journal
- Proceedings of the National Academy of Sciences
- Published
- 2026-10-12
- DOI
- https://doi.org/10.1073/pnas.2616712123
- Primary Topic
- Enzyme function and inhibition
- Type
- article
- Field-Weighted Citation Impact
- 0.00