Molecular Playground/ClyA: Difference between revisions
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<Structure load='1QOY' size='350' frame='true' align='right' caption=' | <Structure load='1QOY' size='350' frame='true' align='right' caption='ClyA complex with sulfate (PDB code [[1qoy]]).' scene='Insert optional scene name here' /> | ||
==Introduction== | ==Introduction== | ||
Pore-forming toxins (PFTs) are virulence factors secreted by pathogenic organisms. These are proteins that form transmembrane channels on target cell membranes. They cause cell death by making the cell membrane permeable, leading to osmotic imbalance and lysis. There are two classes of PFTs based on their secondary structure, alpha-PFTs and beta-PFTs. Cytolysin A (ClyA) is an alpha-PFT and is secreted by ''Salmonella'', ''Shigella'' and ''E. coli'' strains. | Pore-forming toxins (PFTs) are virulence factors secreted by pathogenic organisms. These are proteins that form transmembrane channels on target cell membranes. They cause cell death by making the cell membrane permeable, leading to osmotic imbalance and lysis. There are two classes of PFTs based on their secondary structure, alpha-PFTs and beta-PFTs. '''Cytolysin A (ClyA)''' is an alpha-PFT and is secreted by ''Salmonella'', ''Shigella'' and ''E. coli'' strains. | ||
==About | ==About Cytolysin A== | ||
<scene name='57/571278/Clya_monomer/2'>ClyA monomer in its inactive form</scene> | <scene name='57/571278/Clya_monomer/2'>ClyA monomer in its inactive form</scene> | ||
[[ | [[1qoy]] is a 34 kDa monomer from [http://en.wikipedia.org/wiki/Escherichia_coli ''Escherichia coli''] (''E. coli''). It is an alpha-PFT comprised of four alpha helicies, a smaller fifth alpha helix, and a <B><font color="purple">beta tongue</font></B>. The <B><font color="blue">N-terminus</font></B> and the <B><font color="red">C-terminus</font></B> are highlighted. ClyA has been shown to form pores through a non-classical assembly pathway, excreted in oligomeric form in outer-membrane vesicles (OMV) as pre-pores. Only until ClyA reaches the target host membrane does it form the dodecameric PFT with hemolytic activity, possessing the ability to lyse the host cell. | ||
<scene name='57/571278/Clya_protomer/1'>ClyA protomer</scene> | <scene name='57/571278/Clya_protomer/1'>ClyA protomer</scene> | ||
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The protomer of ClyA reveals slight differences between the monomer and protomer (from the dodecameric oligomer). The major conformational changes between the monomer and the protomer are the positions of the <B><font color="blue">N-terminal helix</font></B> and the <B><font color="purple">beta-tongue</font></B>. As ClyA oligomerizes and forms a pore, the N-terminal helix swings to the opposite side of the molecule while the beta-tongue changes its conformation and turns into an alpha-helix that interacts with the lipid bilayer. | The protomer of ClyA reveals slight differences between the monomer and protomer (from the dodecameric oligomer). The major conformational changes between the monomer and the protomer are the positions of the <B><font color="blue">N-terminal helix</font></B> and the <B><font color="purple">beta-tongue</font></B>. As ClyA oligomerizes and forms a pore, the N-terminal helix swings to the opposite side of the molecule while the beta-tongue changes its conformation and turns into an alpha-helix that interacts with the lipid bilayer. | ||
<scene name='57/571278/Clya_oligomer/ | <scene name='57/571278/Clya_oligomer/3'>The oligomeric form of ClyA with a protomer highlighted in crimson</scene> | ||
Its crystal structure, [[2WCD]], reveals a dodecamer. Larger [http://pubs.acs.org/doi/abs/10.1021/ja4053398 pores] have been isolated, as well. A few research endeavors involving ClyA include using [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2839435/ ClyA as part of cancer therapy], as well as a [http://www.nature.com/ncomms/2013/130912/ncomms3415/full/ncomms3415.html DNA delivery vehicle]. | Its crystal structure, [[2WCD]], reveals a dodecamer. Larger [http://pubs.acs.org/doi/abs/10.1021/ja4053398 pores] have been isolated, as well. A few research endeavors involving ClyA include using [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2839435/ ClyA as part of cancer therapy], as well as a [http://www.nature.com/ncomms/2013/130912/ncomms3415/full/ncomms3415.html DNA delivery vehicle]. | ||
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Current ClyA projects focus on 3 main areas: | Current ClyA projects focus on 3 main areas: | ||
ClyA non-classical assembly and attack | ClyA non-classical assembly and attack | ||