Sandbox WWC1: Difference between revisions

From Proteopedia
Jump to navigationJump to search
← Older editNewer edit →
No edit summary
No edit summary
Line 7: Line 7:


== Background ==
== Background ==
Botulinum Toxin (BTX) is produced by three species of obligate anaerobe bacterium, primarily ''Clostridium botulism'', but ''Clostridium baratii'' and ''Clostridium butyricum'' also produce the protein <ref name="Hall"> PMID: 3988908</ref> <ref name="Aureli"> PMID: 3722863</ref> <ref>Arnon SS. Botulism as an intestinal toxemia. In: Blaser MJ, Smith PD, Ravdin JI, Greenberg HB, Guerrant RL, eds. Infections of the Gastrointestinal Tract. New York, NY: Raven Press; 1995:257-271.</ref>. ''Clostridium botulism'' is commonly found in soil, marine sediments, and the gut of grazing animals <ref name="Ward"> PMID: 5340653</ref> <ref name="Smith"> PMID: 355208</ref> <ref>Sugiyama H. Clostridium botulinum neurotoxin. Microbiol Rev. 1980;44:419–448. 28. Dodds KL. Clostridium botulinum in the environment. In: Hauschild AHW </ref> <ref>Dodds KL, eds. Clostridium botulinum—Ecology and Control in Foods. New York, NY: Marcel Dekker, Inc; 1992: 21–51. 29. </ref> <ref name="Popoff"> PMID: 8542750</ref>  .BTX is only produced by these bacteria when there are anaerobic conditions that induce spore germination. Once produced, the protein can have toxic effects on animals and humans by causing botulism, a potentially fatal illness. BTX is also the active component of Botox.  
Botulinum Toxin (BTX) is produced by three species of obligate anaerobe bacterium, primarily ''Clostridium botulism'', but ''Clostridium baratii'' and ''Clostridium butyricum'' also produce the protein <ref name="Hall"> PMID: 3988908</ref> <ref name="Aureli"> PMID: 3722863</ref> <ref name="Arnon". PMID: 11209178</ref>. ''Clostridium botulism'' is commonly found in soil, marine sediments, and the gut of grazing animals <ref name="Ward"> PMID: 5340653</ref> <ref name="Smith"> PMID: 355208</ref> <ref>Sugiyama H. Clostridium botulinum neurotoxin. Microbiol Rev. 1980;44:419–448. 28. Dodds KL. Clostridium botulinum in the environment. In: Hauschild AHW </ref> <ref>Dodds KL, eds. Clostridium botulinum—Ecology and Control in Foods. New York, NY: Marcel Dekker, Inc; 1992: 21–51. 29. </ref> <ref name="Popoff"> PMID: 8542750</ref>  .BTX is only produced by these bacteria when there are anaerobic conditions that induce spore germination. Once produced, the protein can have toxic effects on animals and humans by causing botulism, a potentially fatal illness. BTX is also the active component of Botox.  
<Structure load='3BTA' size='350' frame='true' align='right' caption='Botulinum Toxin Neurotoxin Serotype A' scene='Insert optional scene name here' />
<Structure load='3BTA' size='350' frame='true' align='right' caption='Botulinum Toxin Neurotoxin Serotype A' scene='Insert optional scene name here' />


Line 13: Line 13:


There are seven forms of the protein, named A through G, that are structurally similar but create different immune responses <ref>  Hatheway cL. Clostridium botulinum and other clostridia that produce botulinum neurotoxins. in: Hauschild aHW, Dodds kL, eds. Clostridium botulinum—Ecology and Control in Foods. new york, ny: marcel Dekker, inc; 1992: 3–10 </ref>. All seven structures are produced as a single chain protein in the bacterium, but becomes active when a protease cuts the protein into a heavy and light chain connected by a single disulfide bond. The heavy chain is approximately 100 kDa and the light chain is 50 kDa (for reviews about structure see references <ref>Sakaguchi G. 1983. Clostridium botulinum toxins. Pharmacol. Ther. 19:165–
There are seven forms of the protein, named A through G, that are structurally similar but create different immune responses <ref>  Hatheway cL. Clostridium botulinum and other clostridia that produce botulinum neurotoxins. in: Hauschild aHW, Dodds kL, eds. Clostridium botulinum—Ecology and Control in Foods. new york, ny: marcel Dekker, inc; 1992: 3–10 </ref>. All seven structures are produced as a single chain protein in the bacterium, but becomes active when a protease cuts the protein into a heavy and light chain connected by a single disulfide bond. The heavy chain is approximately 100 kDa and the light chain is 50 kDa (for reviews about structure see references <ref>Sakaguchi G. 1983. Clostridium botulinum toxins. Pharmacol. Ther. 19:165–
94. </ref> <ref> Minton NP. 1995. Molecular genetics of
94. </ref> <ref name="Minton"> PMID: 8542753</ref> <ref> Oguma K, Fujinaga Y, Inoue K. 1995.Structure and function of Clostridium botulinum toxins. Microbiol. Immunol. 39:161–68 </ref> <ref name="Lacy"> PMID: 10518945</ref> <ref name="Popoff" />).  
clostridial neurotoxins. Curr. Top. Microbiol.
Immunol. 195:161–94 </ref> <ref> Oguma K, Fujinaga Y, Inoue K. 1995.Structure and function of Clostridium botulinum toxins. Microbiol. Immunol. 39:161–68 </ref> <ref name="Lacy"> PMID: 10518945</ref> <ref name="Popoff" />).  


The light chain contains the <scene name='69/696299/Consensus_sequence_heilh/1'>consensus sequence HELIH</scene> that codes for the binding of zinc, which subsequently regulates the endopeptidase activity of the light chain.  
The light chain contains the <scene name='69/696299/Consensus_sequence_heilh/1'>consensus sequence HELIH</scene> that codes for the binding of zinc, which subsequently regulates the endopeptidase activity of the light chain.  
Line 23: Line 21:
== Function ==
== Function ==


The active form of BTX has three functional domains responsible for binding, translocation, and catalysis <ref>Montecucco and Schiavo 1995 C. Montecucco, G. Schiavo Structure and function of tetanus and botulinum neurotoxins Quart. Rev. Biophys., 28 (1995), pp. 423–472. </ref>. The C terminus of the heavy chain is responsible for binding a ganglioside and protein receptors on the nerve terminal while the N terminus half functions by translocating the protein across the membrane by signaling endocytosis <ref>Dolly et al 1984 J.O. Dolly, J. Black, R.S. Williams, J. Melling Acceptors for botulinum neurotoxin reside on motor nerve terminals and mediate its internalization Nature, 307 (1984), pp. 457–460 </ref>. Once in a vesicle in the cytosol of a nerve terminal, the light chain dissociates from the heavy chain and cleaves SNARE proteins involved in synaptic vesicle fusion. The cleavage of these SNARE proteins, VAMP, SNAP-25, and syntax, depends on the serotype of BTX where each serotype cuts at a different place. The cut SNAREs inhibit the binding of vesicles containing acetylcholine which effectively stops the signaling from nerves to muscle cells, resulting in paralysis <ref name="Lacy" />
The active form of BTX has three functional domains responsible for binding, translocation, and catalysis <ref name="Montecucco"> PMID: 8771234</ref>. The C terminus of the heavy chain is responsible for binding a ganglioside and protein receptors on the nerve terminal while the N terminus half functions by translocating the protein across the membrane by signaling endocytosis <ref name="Dolly"> PMID: 6694738</ref>. Once in a vesicle in the cytosol of a nerve terminal, the light chain dissociates from the heavy chain and cleaves SNARE proteins involved in synaptic vesicle fusion. The cleavage of these SNARE proteins, VAMP, SNAP-25, and syntax, depends on the serotype of BTX where each serotype cuts at a different place. The cut SNAREs inhibit the binding of vesicles containing acetylcholine which effectively stops the signaling from nerves to muscle cells, resulting in paralysis <ref name="Lacy" />
</ref>.  
</ref>.  
== Disease ==
== Disease ==
Retrieved from "https://proteopedia.org/Sandbox_WWC1"