Cytosol endopeptidases

Clan CB contains viral chymotrypsin-like cysteine peptidases that process the viral polyproteins, and in clan CC are listed viral papain-like endopeptidases. The only family of clan CD (C14) comprises a number of cytosolic endopeptidases which cleave aspartyl bonds with high specificity. This family of caspases consists of ten members from which caspase-1 and caspase-3 are best known. The mature caspase-... 

The most ingenious exocytosis toxins, however, come from the anaerobic bacteria Clostridium botulinum and Clostridium tetani. The former produces the seven botulinum neurotoxins (BoNTs) A-G the latter produces tetanus neurotoxin (TeNT). All eight toxins consist of a heavy (H) chain and a light (L) chain that are associated by an interchain S-S bond. The L-chains enter the cytosol of axon terminals. Importantly, BoNT L-chains mainly enter peripheral cholinergic terminals, whereas the TeNT L-chain mainly enters cerebral and spinal cord GABAergic and glycinergic terminals. The L-chains are the active domains of the toxins. They are zinc-endopeptidases and specifically split the three core proteins of exocytosis, i.e. the SNAREs (Fig. 1 inset). Each ofthe eight toxins splits a... 

A novel concept of using bioadhesive polymers as enzyme inhibitors has been developed [97]. Included are derivatives of poly acrylic acid, polycarbophil, and car-bomer to protect therapeutically important proteins and peptides from proteolytic activity of enzymes, endopeptidases (trypsin and a-chymotrypsin), exopeptidases (carboxypeptidases A and B), and microsomal and cytosolic leucine aminopeptidase. However, cysteine protease (pyroglutamyl aminopeptidase) is not inhibited by polycarbophil and carbomer [97]. 

Proteasomes rather than cytosolic carboxy-peptidases act to trim the C-terminal amino acids to conform the peptide to the proper size for MHC class-I presentation. Presentation from N-extended precursors is inhibited by acetylation of the terminal a-amino group at the N-terminus [354], which prevents the peptide to be cleaved by aminopeptidases e.g. leucine aminopeptidase) but not by proteasomes or endopeptidases. The TAP system transports peptides to the ER including both mature epitopes and longer precursors. It seems then that the peptides to be presented by MHC class-I can arise from N-extended precursors both in the cytosol and in the endoplasmic reticulum (ER). This assertion has been experimentally confirmed [355,356]. 

Inside the neuronal cytosol, the LC acts as a Zn2+-endopeptidase against specific intracellular protein targets present either on the plasma membrane or on the synaptic vesicle, and inhibits neurotransmitter release by disabling the exocytotic docking/fusion machinery [5,6]. BoNTs catalyze proteolysis of specific proteins of the soluble NSF attachment protein receptor (SNARE) complex that have... 

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