Cholera toxin A2 domain

The **Cholera toxin A2 domain** is a structural domain of the cholera toxin A subunit, a key virulence factor secreted by *Vibrio cholerae*. The full toxin is classified as an AB5-type exotoxin, consisting of one A subunit and five B subunits. The A subunit itself is cleaved into A1 (the enzymatically active domain, responsible for ADP-ribosylation of G proteins in host cells) and A2 domains, which remain linked by a disulfide bond[1][2][3][4][7]. The A2 domain is predominantly alpha-helical and acts as a **tether**, linking the A1 enzymatic domain to the B-pentamer; it passes through the central pore of the doughnut-shaped B-pentamer. The carboxy terminus of the A2 domain (residues Lys-Asp-Glu-Leu; KDEL) interacts with intracellular trafficking machinery, contributing to transit to the endoplasmic reticulum[1][2][3][7]. While critical for the proper assembly and function of cholera toxin, the A2 domain has no known catalytic or direct receptor activity on its own and is not considered a therapeutic target, receptor, enzyme, or transporter[2][3][4][7]. It facilitates non-covalent interactions between the catalytically active A1 domain and the B subunits, enabling the assembly of the holotoxin structure. This entry is flagged as **is_incorrect: true** because the A2 domain itself is not generally considered a druggable target, receptor, enzyme, or independent functional entity—rather, it is a structural tether within a larger toxin complex[2][3][4][7]. The **therapeutically relevant target** in the context of cholera toxin is typically the **entire toxin** (cholera toxin holotoxin or cholera toxin A subunit), not the isolated A2 domain.

Other names

CT-A2A2 domain of cholera toxin