Origin of the Enzymatically Active AI Fragment of Cholera Toxin

Adjuvants modulating mucosal immune responses or directing systemic responses towards the mucosa

“…Both toxins are composed of an A and B subunit of which the B subunit forms a homopentamer structure that binds to epithelial cells. The B subunit of CT and LT binds with high affinity to the glycosphingolipid, GM1-ganglioside (Gal(1-3) GalNAc(1-4)(NeuAc(2-3)Gal(1-4)Glc(1-1) ceramide) [71] and with a lower affinity to GD1b-ganglioside [88]. In addition, LT-B also binds with low affinity to polyglycosylceramides, asialo-GM1, GM2 and polylactosamine-containing glycoproteins [66,89].…”

“…The A subunit is composed of a globular A1 domain and an A2 domain that interacts with the B subunit. The ADPribosyltransferase activity is facilitated following proteolytic cleavage of the trypsin-sensitive loop between the two domains and reduction of the disulfide bond [71]. Then, the A1 fragment enters the cytosol, enzymatically ribosylates the Gs protein of adenylate cyclase, leading to an increased cAMP production.…”

Effects of cholera toxin on innate and adaptive immunity and its application as an immunomodulatory agent

“…The ADPribosyltransferase activity is facilitated following proteolytic cleavage of the trypsin-sensitive loop between the two domains and reduction of the disulphide bond [7]. The A 1 fragment enters the cytosol, and ADP ribosylates the stimulatory ␣ subunit of a guanosine 5Ј-triphosphate (GTP)-binding protein (G s ) that causes permanent activation of the adenylate cyclase, resulting in an elevation in intracellular cyclic adenosine monophosphate (cAMP) concentration [6,9].…”

Changes in tissue cyclic AMP concentrations following an intravenous lethal dose of cholera enterotoxin in rabbits

“…Since this enterotoxin is a protein, its entrance into the cell is based upon the assumption that only the "subunit A" can be transported across the cell membrane [22,23]. According to the present findings, the process of cellular internalization of cholera toxin should not be considered uniform in different body cells.…”