Molecular Playground/ClyA - Revision history

Michal Harel at 11:14, 14 February 2016

Michal Harel — Sun, 14 Feb 2016 11:14:22 GMT

←Older revision		Revision as of 11:14, 14 February 2016
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-	<Structure load='1QOY' size='~~500~~' frame='true' align='right' caption='ClyA complex with sulfate (PDB code [[1qoy]]).' scene='Insert optional scene name here' />	+	<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==

Michal Harel at 11:23, 29 December 2014

Michal Harel — Mon, 29 Dec 2014 11:23:23 GMT

←Older revision		Revision as of 11:23, 29 December 2014
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	<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.	+	[[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>

Michal Harel at 11:23, 29 December 2014

Michal Harel — Mon, 29 Dec 2014 11:23:01 GMT

←Older revision		Revision as of 11:23, 29 December 2014
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-	<Structure load='1QOY' size='500' frame='true' align='right' caption='~~Please select a link from the left to display desired~~ ClyA ~~form~~' scene='Insert optional scene name here' />	+	<Structure load='1QOY' size='500' 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 Cytolysin A==		==About Cytolysin A==

Bib Yang at 03:05, 18 December 2014

Bib Yang — Thu, 18 Dec 2014 03:05:01 GMT

←Older revision		Revision as of 03:05, 18 December 2014
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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/1'>The oligomeric form of ClyA</scene>	+	<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].

Bib Yang at 02:58, 18 December 2014

Bib Yang — Thu, 18 Dec 2014 02:58:15 GMT

←Older revision		Revision as of 02:58, 18 December 2014
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	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 ~~this Structure~~==	+	==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 ~~a pore~~-~~forming toxin (~~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.	+	[[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>

Bib Yang at 22:34, 12 December 2014

Bib Yang — Fri, 12 Dec 2014 22:34:16 GMT

←Older revision		Revision as of 22:34, 12 December 2014
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-	<Structure load='1QOY' size='~~350~~' frame='true' align='right' caption='Please select a link from the left to display desired ClyA form' scene='Insert optional scene name here' />	+	<Structure load='1QOY' size='500' frame='true' align='right' caption='Please select a link from the left to display desired ClyA form' scene='Insert optional scene name here' />
	==Introduction==		==Introduction==

Monifa Fahie at 16:03, 6 December 2014

Monifa Fahie — Sat, 06 Dec 2014 16:03:26 GMT

←Older revision		Revision as of 16:03, 6 December 2014
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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

Monifa Fahie at 16:02, 6 December 2014

Monifa Fahie — Sat, 06 Dec 2014 16:02:46 GMT

←Older revision		Revision as of 16:02, 6 December 2014
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	==Introduction==		==Introduction==

-	~~In progress~~	+	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 this Structure==		==About this Structure==
Line 18:		Line 18:

	==Research on ClyA at UMass Amherst==		==Research on ClyA at UMass Amherst==
-	The Chen Lab~~, in collaboration with the Heuck lab,~~ recently published a paper on [http://www.jbc.org/content/288/43/31042.short, ClyA] assembly. We use a technique commonly used for nanopore sensing called electrophysiology, which allows us to measure the ionic current through the ClyA nanopore.	+	The [http://www.chem.umass.edu/~chenlab/index.HTML, Chen Lab] recently published a paper on [http://www.jbc.org/content/288/43/31042.short, ClyA] non-classical assembly. We use a technique commonly used for nanopore sensing called electrophysiology, which allows us to measure the ionic current through the ClyA nanopore.
		+
		+	Current ClyA projects focus on 3 main areas:
		+	ClyA non-classical assembly and attack
		+
		+	ClyA engineered for cancer therapy
		+
		+	Studies of [http://en.wikipedia.org/wiki/Electro-osmosis, electro-osmosis] using ClyA nanopore

	==References==		==References==

Bib Yang at 21:18, 3 December 2014

Bib Yang — Wed, 03 Dec 2014 21:18:57 GMT

←Older revision		Revision as of 21:18, 3 December 2014
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	==Introduction==		==Introduction==

-		+	In progress

	==About this Structure==		==About this Structure==
	<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 a pore-forming toxin (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.	+	[[1QOY]] is a 34 kDa monomer from [http://en.wikipedia.org/wiki/Escherichia_coli ''Escherichia coli''] (''E. coli''). It is a pore-forming toxin (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>

Bib Yang at 21:18, 3 December 2014

Bib Yang — Wed, 03 Dec 2014 21:18:28 GMT

←Older revision		Revision as of 21:18, 3 December 2014
Line 7:		Line 7:
	<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 a pore-forming toxin (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.	+	[[1QOY]] is a 34 kDa monomer from [http://en.wikipedia.org/wiki/Escherichia_coli ''Escherichia coli''] ''E. coli''. It is a pore-forming toxin (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>