Carbamate post-translational modifications: bridging CO₂ biology and protein regulation

Carbon dioxide (CO₂) is a bioactive gas essential for several physiologically important biological processes, including metabolism, acid-base homoeostasis, and chemosensing. CO₂ can directly modulate these processes by stimulating or inhibiting specific cell signalling pathways, including the nuclear factor-κB, calcium, and Wingless (Wnt) pathways. One mechanism by which CO₂ interacts with proteins to modulate cell signalling is through the reversible and nonenzymatic modification of α- N-terminal and lysine ε-amino groups to form the carbamate post-translational modification (PTM). Identifying carbamate PTMs is technically challenging because these modifications are readily reversible. However, emerging techniques have now made possible their identification and functional characterisation. Here, we review recent advances in experimental and computational methods to identify CO₂-mediated PTMs.