proteins as toxins quick flashcards

what is clostridium botulinum

bacteria that grows on food and produces toxins that cause paralysis when ingested

what do botulism neurtoxins do

prevent neurotransmitters from functioning properly by inhibiting motor control

toxin is an antagonist of acetylcholine

patient experiences paralysis from top to bottom → reaches chest & unable to breathe

what are progenitor toxins

complexes composed of inactive single polypeptide toxin chains and other non toxic accesory proteins

botulism toxins are produced as this before their release via bacterial autolysis

what does the active form of botulism toxins consist of

C-terminal domain - specific presynaptic binding of the toxins

N-terminal domain (L-chain) - Zn2+ dependant endopeptidase

middle domain - translocation of the L-chain into the nerve terminal cytosol

what is the mechanism of action of botulinum toxins

includes cell surface recognition, vesicle internalization, translocation of the catalytic domain (light chain) into the cytosol and proteolytic cleavage of one of the proteins of the SNARE complex

what do botulinum toxins B,D, F and G cleave

proteins of the VAMP family

what do botulinum toxins A, C and E cleave

SNAP-25

C can also cleave syntaxin

what is an antigen

substance capable of stimulating an immune response

botulinum antitoxin

comprised of antibodies or antibody antigen-binding fragments that block the neurotoxin

bind free botulinum toxin, preventing it from being internalized at the post-synpatic cholinergic receptor

only binds to free = not reverse any paralysis already done

what are some applications of botulinum toxin

botulinum toxin A (botox) are used in plastic surgery

it’s highly specific for peripheral cholinergic nerve terminals and doesn’t spread much from site of injection

action is reversible but can last for up to 6 months

what are limitations of botulinum neurotoxins

could elicit neutralizing antibodies against the toxin, reducing the beneficial effects or rendering the patient unresponsive to further treatment

what is cholera toxin

a protein (enterotoxin) secreted from vibrio cholera (bacterium)

what is cholera

potentially epidemic, life threatening diarrhoea

vomiting, resulting in hypovolemic shock and acidosis

what does cholera toxin do

affects epithelial cells in intestine

causes over activation of chloride channel proteins activity and activates them to open and allow mvmt of Cl- out of the cell in absence of the signalling molecule

what is the structure of cholera toxin

subunit A - A1 domain includes the enzymatic active site, A2 domain has a alpha-helix tail

subunit B - has 5 chains that form a pentameric ring around the central pore in structure

both subunits assembled by the a-helix tail of A2 which inserts into the central pore

what is the mechanism of action of cholera toxin

binds to ganglioside receptors on surface of intestinal epithelium cells → internalised by endocytosis → production of cyclic AMP (a second messanger) within the cell

what does cyclic AMP do

activates specific ion channels in cell membrane, causing efflux of ions from cell

build up of ions in intestinal lumen draws water from cells and tissues via osmosis - causing acute diarrhoea