Group:SMART:Tangible Models of Cdc42 Interacting With Intersectin - Revision history

Judy Voet at 08:32, 9 November 2009

2009-11-09T08:32:57Z

← Older revision		Revision as of 08:32, 9 November 2009
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	:Information transfer within the cell relies upon signaling pathways made up of interacting proteins. Rho-family [[GTPase]]s are GTP-binding proteins, which function as molecular switches initially in the "off" state. Interactions with activators turn these GTPases "on" and they then interact with other proteins, leading to a variety of cellular behaviors such as directed movement and changes in cell shape.		:Information transfer within the cell relies upon signaling pathways made up of interacting proteins. Rho-family [[GTPase]]s are GTP-binding proteins, which function as molecular switches initially in the "off" state. Interactions with activators turn these GTPases "on" and they then interact with other proteins, leading to a variety of cellular behaviors such as directed movement and changes in cell shape.

	:Traditional methods for visualizing protein structures and interactions are often limited in the amount of information that can be conveyed in two dimensions. Using the rapid prototyping technology at the Milwaukee School of Engineering's Center for BioMolecular Modeling, we have built tangible 3D models of the Rho GTPase Cdc42 in complex with one of its activators. Our model shows the interaction of Cdc42 with the catalytic domains of intersectin, based upon the published crystal structure solved by Snyder, et al (PDB 1KI1, Nature Structural Biology 2002; 9(6): 468- 475). Along with computer visualization tools, tangible 3D models allow students and scientists alike to more fully explore the intricacies of protein interactions.		:Traditional methods for visualizing protein structures and interactions are often limited in the amount of information that can be conveyed in two dimensions. Using the rapid prototyping technology at the Milwaukee School of Engineering's Center for BioMolecular Modeling, we have built tangible 3D models of the Rho GTPase [http://en.wikipedia.org/wiki/CDC42 Cdc42] in complex with one of its activators. Our model shows the interaction of Cdc42 with the catalytic domains of intersectin, based upon the published crystal structure solved by Snyder, et al (PDB 1KI1, Nature Structural Biology 2002; 9(6): 468- 475). Along with computer visualization tools, tangible 3D models allow students and scientists alike to more fully explore the intricacies of protein interactions.

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Kurt Giles at 23:27, 29 April 2009

2009-04-29T23:27:05Z

← Older revision		Revision as of 23:27, 29 April 2009
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	~~='''<font color = 'black'> Tangible Models of Cdc42 Interacting With Intersectin </font>'''=~~

	=='''<font color = 'red'>A Lincoln HS SMART Team Telling a Molecular Story</font><font color = 'black'></font>'''==		=='''<font color = 'red'>A Lincoln HS SMART Team Telling a Molecular Story</font><font color = 'black'></font>'''==
	[[Image:Lincoln Team 2008.JPG\|left\|360px]]		[[Image:Lincoln Team 2008.JPG\|left\|360px]]

Kurt Giles: SMART Lincoln 2009 moved to Tangible Models of Cdc42 Interacting With Intersectin: This was the 2008 team project. The new title represents the topic of the page

2009-04-29T23:26:22Z

SMART Lincoln 2009 moved to Tangible Models of Cdc42 Interacting With Intersectin: This was the 2008 team project. The new title represents the topic of the page

← Older revision	Revision as of 23:26, 29 April 2009
(No difference)

Elizaveta Sergeeva at 11:21, 8 February 2009

2009-02-08T11:21:14Z

← Older revision		Revision as of 11:21, 8 February 2009
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	1) <scene name='SMART_Lincoln_2009/Cdc42_and_gdp/1'>Cdc42</scene> (<font color = '#FFFF00'><b> yellow </b></font>) is off when GDP is in its binding pocket. <font color = '#FF1493'><b> Mg++ </b></font>is shown in magenta, <font color = '#00FF00'><b> Alanine 59 </b></font> in green, <font color = '#FFA500'><b>Switch 1</b></font> in light gold, and <font color = '#FF6600'><b>Switch 2</b></font> in dark orange. Brown depicts the residues interacting with <font color = '#~~8B4513~~'><b>GDP</b></font> (<font color = '#8B4513'><b>Lys16 and Cys18</b></font>).		1) <scene name='SMART_Lincoln_2009/Cdc42_and_gdp/1'>Cdc42</scene> (<font color = '#FFFF00'><b> yellow </b></font>) is off when GDP is in its binding pocket. <font color = '#FF1493'><b> Mg++ </b></font>is shown in magenta, <font color = '#00FF00'><b> Alanine 59 </b></font> in green, <font color = '#FFA500'><b>Switch 1</b></font> in light gold, and <font color = '#FF6600'><b>Switch 2</b></font> in dark orange. Brown depicts the residues interacting with <font color = '#00BFFF'><b>GDP</b></font> (<font color = '#8B4513'><b>Lys16 and Cys18</b></font>).


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	3) Thee interaction causes conformational changes in <font color = '#FFA500'><b>Switch 1</b></font> and <font color = '#FF6600'><b>Switch 2</b></font> of Cdc42. <font color = '#FF0000'><b>Thr35</b></font> hydrogen bonds to a residue (<font color = '#802AAB'><b>Glu1244</b></font>) of the <font color = '#6A5ACD'><b>DH domain</b></font> of Intersectin. Most important is the noticeable change in the orientation of residue 59 (<font color = '#00FF00'><b>Ala59</b></font>). Its sidechain flips into the magnesium-binding pocket, causing the release of the <font color = '#FF1493'><b> Mg++ </b></font> ion and in turn the release of <font color = '#~~8B4513~~'><b>GDP</b></font> from <font color = '#FFFF00'><b>Cdc42</b></font>.		3) Thee interaction causes conformational changes in <font color = '#FFA500'><b>Switch 1</b></font> and <font color = '#FF6600'><b>Switch 2</b></font> of Cdc42. <font color = '#FF0000'><b>Thr35</b></font> hydrogen bonds to a residue (<font color = '#802AAB'><b>Glu1244</b></font>) of the <font color = '#6A5ACD'><b>DH domain</b></font> of Intersectin. Most important is the noticeable change in the orientation of residue 59 (<font color = '#00FF00'><b>Ala59</b></font>). Its sidechain flips into the magnesium-binding pocket, causing the release of the <font color = '#FF1493'><b> Mg++ </b></font> ion and in turn the release of <font color = '#00BFFF'><b>GDP</b></font> from <font color = '#FFFF00'><b>Cdc42</b></font>.


	4) <font color = '#FF1493'><b> Mg++ </b></font> and <font color = '#~~8B4513~~'><b>GDP</b></font> fall off from <font color = '#FFFF00'><b> Cdc42</b></font>. The nucleotide-binding pocket of <font color = '#FFFF00'><b>Cdc42</b></font> is now empty.		4) <font color = '#FF1493'><b> Mg++ </b></font> and <font color = '#00BFFF'><b>GDP</b></font> fall off from <font color = '#FFFF00'><b> Cdc42</b></font>. The nucleotide-binding pocket of <font color = '#FFFF00'><b>Cdc42</b></font> is now empty.


	5) Because the intracellular ratio of <font color = '#2F6E46'><b>GTP</b></font> to <font color = '#~~8B4513~~'><b>GDP</b></font> is high, a <font color = '#2F6E46'><b>GTP</b></font> molecule (dark green) will float into the binding pocket of <font color = '#FFFF00'><b>Cdc42</b></font> and activate it.		5) Because the intracellular ratio of <font color = '#2F6E46'><b>GTP</b></font> to <font color = '#00BFFF'><b>GDP</b></font> is high, a <font color = '#2F6E46'><b>GTP</b></font> molecule (dark green) will float into the binding pocket of <font color = '#FFFF00'><b>Cdc42</b></font> and activate it.





			{{Clear}}

			==''<font color = 'black'>Animation: How Intersectin Activates Cdc42</font>''==



			{{Clear}}

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Elizaveta Sergeeva at 09:34, 8 February 2009

2009-02-08T09:34:42Z

← Older revision		Revision as of 09:34, 8 February 2009
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	=='''<font color = 'red'>A Lincoln HS SMART Team Telling a Molecular Story</font><font color = 'black'></font>'''==		=='''<font color = 'red'>A Lincoln HS SMART Team Telling a Molecular Story</font><font color = 'black'></font>'''==
			[[Image:Lincoln Team 2008.JPG\|left\|360px]]

	~~Abraham Lincoln High School, San Francisco, California~~
	~~:Students -- Cyndi He, Glen Huynh, Aissa Isana, Bradley Jann, Bradford Li, Yaqiao Li, Calvin Ng, Tiffany Saw, Elizaveta Sergeeva, Jacqueline Tam, Allison Trinh, Michelle Xie, Ellen Zhang~~
	~~:Teacher -- Julie Reis~~

	Mentors:		<font color = 'red'><b>Abraham Lincoln High School, San Francisco, California</b></font>
	:UCSF Science and Health Education Partnership -- Sabine Jeske		:<b>Students</b> -- Cyndi He, Glen Huynh, Aissa Isana, Bradley Jann, Bradford Li, Yaqiao Li, Calvin Ng, Tiffany Saw, Elizaveta Sergeeva, Jacqueline Tam, Allison Trinh, Michelle Xie, Ellen Zhang
	:UCSF/UCB Joint Graduate Group in Bioengineering -- Angela Chau		:<b>Teacher</b> -- Julie Reis
	:Institute for Neurodegenerative Diseases, UCSF -- Kurt Giles
	:Center for BioMolecular Modeling, Milwaukee School of Engineering -- Shannondoah Colton
			<font color = 'blue'><b>Mentors:</b></font>
			:<b>UCSF Science and Health Education Partnership</b> -- Sabine Jeske
			:<b>UCSF/UCB Joint Graduate Group in Bioengineering</b> -- Angela Chau
			:<b>Institute for Neurodegenerative Diseases, UCSF</b> -- Kurt Giles
			:<b>Center for BioMolecular Modeling, Milwaukee School of Engineering</b> -- Shannondoah Colton


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	='''<font color = 'black'>Abstract for Our Project</font>'''=		='''<font color = 'black'>Abstract for Our Project</font>'''=


	==<font color = 'blue'>Abstract</font>==		==<font color = 'blue'>Abstract</font>==
			[[Image:Poster picture.jpg\|right\|380px]]

	:Information transfer within the cell relies upon signaling pathways made up of interacting proteins. Rho-family [[GTPase]]s are GTP-binding proteins, which function as molecular switches initially in the "off" state. Interactions with activators turn these GTPases "on" and they then interact with other proteins, leading to a variety of cellular behaviors such as directed movement and changes in cell shape.		:Information transfer within the cell relies upon signaling pathways made up of interacting proteins. Rho-family [[GTPase]]s are GTP-binding proteins, which function as molecular switches initially in the "off" state. Interactions with activators turn these GTPases "on" and they then interact with other proteins, leading to a variety of cellular behaviors such as directed movement and changes in cell shape.
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	==<font color = 'blue'>Cell Signaling and Cell Movement</font>==		==<font color = 'blue'>Cell Signaling and Cell Movement</font>==
	[[Image:Filopodia.jpg\|left\|250px]]		[[Image:Filopodia.jpg\|left\|250px]]


	:[[Cell signaling]] is how cells transmit information from the outside environment to inside the cell as well as how cells propagate messages within the cell. Transmembrane receptors at the cell surface detect environmental changes and pass the information on to intracellular signaling proteins. Proteins that make up signaling pathways pass along messages by interacting with each other.		:[[Cell signaling]] is how cells transmit information from the outside environment to inside the cell as well as how cells propagate messages within the cell. Transmembrane receptors at the cell surface detect environmental changes and pass the information on to intracellular signaling proteins. Proteins that make up signaling pathways pass along messages by interacting with each other.
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	==<font color = 'blue'>Why build a model?</font>==		==<font color = 'blue'>Why build a model?</font>==
			[[Image:Actual 3d models.JPG\|right\|150px]]


	:A 3-dimensional model generated by the polymer printing technology at the Center for BioMolecular Modeling greatly enhances our ability to visualize and explore Cdc42 and its interaction with Intersectin. The complex structures and shapes of these molecules can be appreciated more fully through seeing and touching a physical model. A tangible model can not only aid us in summarizing what we know but can also inspire us and other scientists to ask new questions and come up with new hypotheses about these molecules.		:A 3-dimensional model generated by the polymer printing technology at the Center for BioMolecular Modeling greatly enhances our ability to visualize and explore Cdc42 and its interaction with Intersectin. The complex structures and shapes of these molecules can be appreciated more fully through seeing and touching a physical model. A tangible model can not only aid us in summarizing what we know but can also inspire us and other scientists to ask new questions and come up with new hypotheses about these molecules.


	{{clear}}		{{clear}}

	='''<font color = 'black'>Cdc42: The GTPase</font>'''=		='''<font color = 'black'>Cdc42: The GTPase</font>'''=

	[[Image:GDP to GTP.jpg\|right\|250px]]		[[Image:GDP to GTP.jpg\|right\|250px]]

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	:<scene name='SMART_Lincoln_2009/Complex_intersectin_and_cdc42/1'>Cdc42/Intersectin Complex.</scene> The orientation of Alanine 59 is the highlight of Cdc42 activation by Intersectin. Alanine 59 causes the displacement of the Mg++ ion which in turn releases GDP from Cdc42’s binding pocket. Cdc42 is then able to accept a new nucleotide, specifically GTP, to become activated.		:<scene name='SMART_Lincoln_2009/Complex_intersectin_and_cdc42/1'>Cdc42/Intersectin Complex.</scene> The orientation of Alanine 59 is the highlight of Cdc42 activation by Intersectin. Alanine 59 causes the displacement of the Mg++ ion which in turn releases GDP from Cdc42’s binding pocket. Cdc42 is then able to accept a new nucleotide, specifically GTP, to become activated.

	<applet load='2rh1.pdb' size='350' frame='true' align='~~left~~' scene='SMART_Lincoln_2009/Complex_intersectin_and_cdc42/1'/>		<applet load='2rh1.pdb' size='350' frame='true' align='right' scene='SMART_Lincoln_2009/Complex_intersectin_and_cdc42/1'/>


	1) <scene name='SMART_Lincoln_2009/Cdc42_and_gdp/1'>Cdc42</scene> (yellow) is off when GDP is in its binding pocket. Mg++ is shown in magenta, Alanine 59 in green, Switch 1 in light gold, and Switch 2 in dark orange. Brown depicts the residues interacting with GDP (Lys16 and Cys18).		1) <scene name='SMART_Lincoln_2009/Cdc42_and_gdp/1'>Cdc42</scene> (<font color = '#FFFF00'><b> yellow </b></font>) is off when GDP is in its binding pocket. <font color = '#FF1493'><b> Mg++ </b></font>is shown in magenta, <font color = '#00FF00'><b> Alanine 59 </b></font> in green, <font color = '#FFA500'><b>Switch 1</b></font> in light gold, and <font color = '#FF6600'><b>Switch 2</b></font> in dark orange. Brown depicts the residues interacting with <font color = '#8B4513'><b>GDP</b></font> (<font color = '#8B4513'><b>Lys16 and Cys18</b></font>).

	~~2) <scene name='SMART_Lincoln_2009/Complex_intersectin_and_cdc42/1'>Intersectin</scene>(blue) binds to Cdc42, and its DH domain interacts with the GTPase.~~

	3) ~~Thee interaction causes conformational changes in Switch~~ 1 ~~and Switch 2 of Cdc42. _r35 hydrogen bonds to a residue (Glu1244) of the DH domain of~~ Intersectin~~. Most important is the noticeable change in the orientation of residue 59~~ (~~Ala59~~)~~. Its sidechain flips into the magnesium-binding pocket~~, ~~causing the release of the Mg++ ion~~ and ~~in turn~~ the ~~release of GDP from Cdc42~~.		2) <scene name='SMART_Lincoln_2009/Complex_intersectin_and_cdc42/1'>Intersectin</scene>(blue) binds to <font color = '#FFFF00'><b>Cdc42</b></font>, and its <font color = '#6A5ACD'><b>DH domain</b></font> interacts with the GTPase.

	~~4) Mg++ and GDP fall off from Cdc42. the nucleotide-binding pocket of Cdc42 is now empty.~~

	5) ~~Because~~ the ~~intracellular ratio~~ of ~~GTP to GDP~~ is ~~high, a GTP molecule~~ (~~dark green~~) ~~will float~~ into the binding pocket of Cdc42 ~~and activate it~~.		3) Thee interaction causes conformational changes in <font color = '#FFA500'><b>Switch 1</b></font> and <font color = '#FF6600'><b>Switch 2</b></font> of Cdc42. <font color = '#FF0000'><b>Thr35</b></font> hydrogen bonds to a residue (<font color = '#802AAB'><b>Glu1244</b></font>) of the <font color = '#6A5ACD'><b>DH domain</b></font> of Intersectin. Most important is the noticeable change in the orientation of residue 59 (<font color = '#00FF00'><b>Ala59</b></font>). Its sidechain flips into the magnesium-binding pocket, causing the release of the <font color = '#FF1493'><b> Mg++ </b></font> ion and in turn the release of <font color = '#8B4513'><b>GDP</b></font> from <font color = '#FFFF00'><b>Cdc42</b></font>.


			4) <font color = '#FF1493'><b> Mg++ </b></font> and <font color = '#8B4513'><b>GDP</b></font> fall off from <font color = '#FFFF00'><b> Cdc42</b></font>. The nucleotide-binding pocket of <font color = '#FFFF00'><b>Cdc42</b></font> is now empty.


			5) Because the intracellular ratio of <font color = '#2F6E46'><b>GTP</b></font> to <font color = '#8B4513'><b>GDP</b></font> is high, a <font color = '#2F6E46'><b>GTP</b></font> molecule (dark green) will float into the binding pocket of <font color = '#FFFF00'><b>Cdc42</b></font> and activate it.

Elizaveta Sergeeva at 12:13, 7 February 2009

2009-02-07T12:13:00Z

← Older revision		Revision as of 12:13, 7 February 2009
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	=='''<font color = 'red'>A Lincoln HS SMART Team Telling a Molecular Story</font><font color = 'black'></font>'''==		=='''<font color = 'red'>A Lincoln HS SMART Team Telling a Molecular Story</font><font color = 'black'></font>'''==

	:Abraham Lincoln High School, San Francisco, California		Abraham Lincoln High School, San Francisco, California
	:Students -- Cyndi He, Glen Huynh, Aissa Isana, Bradley Jann, Bradford Li, Yaqiao Li, Calvin Ng, Tiffany Saw, Elizaveta Sergeeva, Jacqueline Tam, Allison Trinh, Michelle Xie, Ellen Zhang		:Students -- Cyndi He, Glen Huynh, Aissa Isana, Bradley Jann, Bradford Li, Yaqiao Li, Calvin Ng, Tiffany Saw, Elizaveta Sergeeva, Jacqueline Tam, Allison Trinh, Michelle Xie, Ellen Zhang
	:Teacher -- Julie Reis		:Teacher -- Julie Reis

	:Mentors:		Mentors:
	:UCSF Science and Health Education Partnership -- Sabine Jeske		:UCSF Science and Health Education Partnership -- Sabine Jeske
	:UCSF/UCB Joint Graduate Group in Bioengineering -- Angela Chau		:UCSF/UCB Joint Graduate Group in Bioengineering -- Angela Chau
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	==<font color = 'blue'>Abstract</font>==		==<font color = 'blue'>Abstract</font>==

	Information transfer within the cell relies upon signaling pathways made up of interacting proteins. Rho-family ~~GTPases~~ are GTP-binding proteins, which function as molecular switches initially in the "off" state. Interactions with activators turn these GTPases "on" and they then interact with other proteins, leading to a variety of cellular behaviors such as directed movement and changes in cell shape.		:Information transfer within the cell relies upon signaling pathways made up of interacting proteins. Rho-family [[GTPase]]s are GTP-binding proteins, which function as molecular switches initially in the "off" state. Interactions with activators turn these GTPases "on" and they then interact with other proteins, leading to a variety of cellular behaviors such as directed movement and changes in cell shape.

	Traditional methods for visualizing protein structures and interactions are often limited in the amount of information that can be conveyed in two dimensions. Using the rapid prototyping technology at the Milwaukee School of Engineering's Center for BioMolecular Modeling, we have built tangible 3D models of the Rho GTPase Cdc42 in complex with one of its activators. Our model shows the interaction of Cdc42 with the catalytic domains of intersectin, based upon the published crystal structure solved by Snyder, et al (PDB 1KI1, Nature Structural Biology 2002; 9(6): 468- 475). Along with computer visualization tools, tangible 3D models allow students and scientists alike to more fully explore the intricacies of protein interactions.		:Traditional methods for visualizing protein structures and interactions are often limited in the amount of information that can be conveyed in two dimensions. Using the rapid prototyping technology at the Milwaukee School of Engineering's Center for BioMolecular Modeling, we have built tangible 3D models of the Rho GTPase Cdc42 in complex with one of its activators. Our model shows the interaction of Cdc42 with the catalytic domains of intersectin, based upon the published crystal structure solved by Snyder, et al (PDB 1KI1, Nature Structural Biology 2002; 9(6): 468- 475). Along with computer visualization tools, tangible 3D models allow students and scientists alike to more fully explore the intricacies of protein interactions.

	{{clear}}		{{clear}}
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	[[Image:Filopodia.jpg\|left\|250px]]		[[Image:Filopodia.jpg\|left\|250px]]

	Cell signaling is how cells transmit information from the outside environment to inside the cell as well as how cells propagate messages within the cell. Transmembrane receptors at the cell surface detect environmental changes and pass the information on to intracellular signaling proteins. Proteins that make up signaling pathways pass along messages by interacting with each other.		:[[Cell signaling]] is how cells transmit information from the outside environment to inside the cell as well as how cells propagate messages within the cell. Transmembrane receptors at the cell surface detect environmental changes and pass the information on to intracellular signaling proteins. Proteins that make up signaling pathways pass along messages by interacting with each other.

	Cell movement is integral for survival in both bacterial and eukaryotic cells. In eukaryotes, cells move by changing their ~~cytoskeletons~~ to form actin structures like filopodia. These structures are formed in response to signals from outside of cells which are relayed throughout the cell using signaling pathways.		:Cell movement is integral for survival in both bacterial and eukaryotic cells. In eukaryotes, cells move by changing their [[cytoskeleton]]s to form [[actin]] structures like filopodia. These structures are formed in response to signals from outside of cells which are relayed throughout the cell using signaling pathways.

	{{clear}}		{{clear}}
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	==<font color = 'blue'>Why build a model?</font>==		==<font color = 'blue'>Why build a model?</font>==

	A 3-dimensional model generated by the polymer printing technology at the Center for BioMolecular Modeling greatly enhances our ability to visualize and explore Cdc42 and its interaction with Intersectin. _e complex structures and shapes of these molecules can be appreciated more fully through seeing and touching a physical model. A tangible model can not only aid us in summarizing what we know but can also inspire us and other scientists to ask new questions and come up with new ~~hypothesesabout~~ these molecules.		:A 3-dimensional model generated by the polymer printing technology at the Center for BioMolecular Modeling greatly enhances our ability to visualize and explore Cdc42 and its interaction with Intersectin. The complex structures and shapes of these molecules can be appreciated more fully through seeing and touching a physical model. A tangible model can not only aid us in summarizing what we know but can also inspire us and other scientists to ask new questions and come up with new hypotheses about these molecules.


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	[[Image:GDP to GTP.jpg\|right\|250px]]		[[Image:GDP to GTP.jpg\|right\|250px]]

	Like other Rho GTPases, <scene name='SMART_Lincoln_2009/Cdc42_and_gdp/1'>Cdc42</scene> can exist in either the “Off” or “On” state. A ~~guanine~~ diphosphate (GDP) in the nucleotide-binding pocket indicates the “Off” state, and a ~~guanine~~ triphosphate (GTP) indicates the “On” state. _e activation from the “Off” state to the “On” state is catalyzed by a guanine-nucleotide exchange factor (GEF). Thee hydrolysis of GTP, which turns the GTPase off, is catalyzed by a GTPase activating protein called a GAP.		:Like other Rho GTPases, <scene name='SMART_Lincoln_2009/Cdc42_and_gdp/1'>Cdc42</scene> can exist in either the “Off” or “On” state. A [[guanosine diphosphate]] (GDP) in the nucleotide-binding pocket indicates the “Off” state, and a [[guanosine triphosphate]] (GTP) indicates the “On” state. The activation from the “Off” state to the “On” state is catalyzed by a [[guanine nucleotide exchange factor]] (GEF). Thee hydrolysis of GTP, which turns the GTPase off, is catalyzed by a GTPase activating protein called a GAP.

	In addition to binding to a nucleotide (GDP or GTP), Cdc42 is usually found to be bound to a magnesium ion (Mg++), shown in magenta. The Mg++ sits near the nucleotide-binding pocket and helps to stabilize the Cdc42-nucleotide interaction.		:In addition to binding to a nucleotide (GDP or GTP), Cdc42 is usually found to be bound to a magnesium ion (Mg++), shown in magenta. The Mg++ sits near the nucleotide-binding pocket and helps to stabilize the Cdc42-nucleotide interaction.

	{{clear}}		{{clear}}
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	='''<font color = 'black'>Intersectin - The GEF</font>'''=		='''<font color = 'black'>Intersectin - The GEF</font>'''=

	Intersectin is one of the activators of the GTPase Cdc42. It is a guanine nucleotide exchange factor (GEF) and turns on Cdc42 by catalyzing the exchange of GDP for GTP. Intersectin is a signaling protein that contains many domains, not all of which are shown here. The structure of the Cdc42/Intersectin complex was solved with the DH (residues 1229- 1439) and PH (residues 1440-1580) domains of Intersectin. Here, we focus only on the DH domain because the PH domain does not appear to come into any significant contact with Cdc42.		:Intersectin is one of the activators of the GTPase Cdc42. It is a guanine nucleotide exchange factor (GEF) and turns on Cdc42 by catalyzing the exchange of GDP for GTP. Intersectin is a signaling protein that contains many domains, not all of which are shown here. The structure of the Cdc42/Intersectin complex was solved with the DH (residues 1229- 1439) and PH (residues 1440-1580) domains of Intersectin. Here, we focus only on the DH domain because the PH domain does not appear to come into any significant contact with Cdc42.

	{{clear}}		{{clear}}
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	='''<font color = 'black'>How Intersectin Activates Cdc42</font>'''=		='''<font color = 'black'>How Intersectin Activates Cdc42</font>'''=

	<scene name='SMART_Lincoln_2009/Complex_intersectin_and_cdc42/1'>Cdc42/Intersectin Complex.</scene> The orientation of Alanine 59 is the highlight of Cdc42 activation by Intersectin. Alanine 59 causes the displacement of the Mg++ ion which in turn releases GDP from Cdc42’s binding pocket. Cdc42 is then able to accept a new nucleotide, specifically GTP, to become activated.		:<scene name='SMART_Lincoln_2009/Complex_intersectin_and_cdc42/1'>Cdc42/Intersectin Complex.</scene> The orientation of Alanine 59 is the highlight of Cdc42 activation by Intersectin. Alanine 59 causes the displacement of the Mg++ ion which in turn releases GDP from Cdc42’s binding pocket. Cdc42 is then able to accept a new nucleotide, specifically GTP, to become activated.

	<applet load='2rh1.pdb' size='350' frame='true' align='left' scene='SMART_Lincoln_2009/Complex_intersectin_and_cdc42/1'/>		<applet load='2rh1.pdb' size='350' frame='true' align='left' scene='SMART_Lincoln_2009/Complex_intersectin_and_cdc42/1'/>
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	5) Because the intracellular ratio of GTP to GDP is high, a GTP molecule (dark green) will float into the binding pocket of Cdc42 and activate it.		5) Because the intracellular ratio of GTP to GDP is high, a GTP molecule (dark green) will float into the binding pocket of Cdc42 and activate it.

Elizaveta Sergeeva at 11:47, 7 February 2009

2009-02-07T11:47:04Z

← Older revision		Revision as of 11:47, 7 February 2009
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	Cell signaling is how cells transmit information from the outside environment to inside the cell as well as how cells propagate messages within the cell. Transmembrane receptors at the cell surface detect environmental changes and pass the information on to intracellular signaling proteins. Proteins that make up signaling pathways pass along messages by interacting with each other.		Cell signaling is how cells transmit information from the outside environment to inside the cell as well as how cells propagate messages within the cell. Transmembrane receptors at the cell surface detect environmental changes and pass the information on to intracellular signaling proteins. Proteins that make up signaling pathways pass along messages by interacting with each other.

	Cell movement is integral for survival in both bacterial and eukaryotic cells. In eukaryotes, cells move by changing their cytoskeletons to form actin structures like filopodia. ~~_ese~~ structures are formed in response to signals from outside of cells which are relayed throughout the cell using signaling pathways.		Cell movement is integral for survival in both bacterial and eukaryotic cells. In eukaryotes, cells move by changing their cytoskeletons to form actin structures like filopodia. These structures are formed in response to signals from outside of cells which are relayed throughout the cell using signaling pathways.

	{{clear}}		{{clear}}
Line 61:		Line 61:
	='''<font color = 'black'>How Intersectin Activates Cdc42</font>'''=		='''<font color = 'black'>How Intersectin Activates Cdc42</font>'''=

	<scene name='SMART_Lincoln_2009/Complex_intersectin_and_cdc42/1'>Cdc42/Intersectin Complex</scene>		<scene name='SMART_Lincoln_2009/Complex_intersectin_and_cdc42/1'>Cdc42/Intersectin Complex.</scene> The orientation of Alanine 59 is the highlight of Cdc42 activation by Intersectin. Alanine 59 causes the displacement of the Mg++ ion which in turn releases GDP from Cdc42’s binding pocket. Cdc42 is then able to accept a new nucleotide, specifically GTP, to become activated.
	The orientation of Alanine 59 is the highlight of Cdc42 activation by Intersectin. Alanine 59 causes the displacement of the Mg++ ion which in turn releases GDP from Cdc42’s binding pocket. Cdc42 is then able to accept a new nucleotide, specifically GTP, to become activated.

	<applet load='2rh1.pdb' size='350' frame='true' align='left' scene='SMART_Lincoln_2009/Complex_intersectin_and_cdc42/1'/>		<applet load='2rh1.pdb' size='350' frame='true' align='left' scene='SMART_Lincoln_2009/Complex_intersectin_and_cdc42/1'/>

	-- <scene name='SMART_Lincoln_2009/Cdc42_and_gdp/1'>Cdc42</scene> (yellow) is off when GDP is in its binding pocket. Mg++ is shown in magenta, Alanine 59 in green, Switch 1 in light gold, and Switch 2 in dark orange. Brown depicts the residues interacting with GDP (Lys16 and Cys18).		1) <scene name='SMART_Lincoln_2009/Cdc42_and_gdp/1'>Cdc42</scene> (yellow) is off when GDP is in its binding pocket. Mg++ is shown in magenta, Alanine 59 in green, Switch 1 in light gold, and Switch 2 in dark orange. Brown depicts the residues interacting with GDP (Lys16 and Cys18).

			2) <scene name='SMART_Lincoln_2009/Complex_intersectin_and_cdc42/1'>Intersectin</scene>(blue) binds to Cdc42, and its DH domain interacts with the GTPase.

			3) Thee interaction causes conformational changes in Switch 1 and Switch 2 of Cdc42. _r35 hydrogen bonds to a residue (Glu1244) of the DH domain of Intersectin. Most important is the noticeable change in the orientation of residue 59 (Ala59). Its sidechain flips into the magnesium-binding pocket, causing the release of the Mg++ ion and in turn the release of GDP from Cdc42.

			4) Mg++ and GDP fall off from Cdc42. the nucleotide-binding pocket of Cdc42 is now empty.

			5) Because the intracellular ratio of GTP to GDP is high, a GTP molecule (dark green) will float into the binding pocket of Cdc42 and activate it.





	~~-- <scene name='SMART_Lincoln_2009/Complex_intersectin_and_cdc42/1'>Cdc42/Intersectin Complex</scene>Intersectin (blue) binds to Cdc42, and its DH domain interacts with the GTPase.~~

	-- Thee interaction causes conformational changes in Switch 1 and Switch 2 of Cdc42. _r35 hydrogen bonds to a residue (Glu1244) of the DH domain of Intersectin. Most important is the noticeable change in the orientation of residue 59 (Ala59). Its sidechain flips into the magnesium-binding pocket, causing the release of the Mg++ ion and in turn the release of GDP from Cdc42.

	~~-- Mg++ and GDP fall off from Cdc42. the nucleotide-binding pocket of Cdc42 is now empty.~~

	~~-- Because the intracellular ratio of GTP to GDP is high, a GTP molecule (dark green) will float into the binding pocket of Cdc42 and activate it.~~


Line 80:		Line 87:
	----		----

	==<font color = 'red'>MSOE Center for BioMolecular Modeling and SMART Teams</font>==		=<font color = 'red'>MSOE Center for BioMolecular Modeling and SMART Teams</font>=
	[[Image:Center for BioMolecular Modeling Logo.jpg\|left\|200px]]		[[Image:Center for BioMolecular Modeling Logo.jpg\|left\|200px]]
	[[Image:Smart Teams photo 5.jpg\|right\|120px]]		[[Image:Smart Teams photo 5.jpg\|right\|120px]]

	<font color = 'red'>SMART Teams (S</font>tudents <font color = 'red'>M</font>odeling <font color = 'red'>A</font> <font color = 'red'>R</font>esearch <font color = 'red'>T</font>opic) is a science outreach program developed by the MSOE Center for BioMolecular Modeling. In this program, teams of high school students work with a local resarch lab to design and build a physical model of a protein that is being investigated by the lab. The goal of the SMART Team program is to introduce students to the real world of scince --- as it exists in a local research lab. The development of this program was supported by grants from the NIH-NCRR SEPA program (Science Education Partnership Award) and an HHMI Precollege Science Education Award. For more information about this program, visit the CBM web site at [http://www.rpc.msoe.edu/cbm www.rpc.msoe.edu/cbm] .		<font color = 'red'>SMART Teams (S</font>tudents <font color = 'red'>M</font>odeling <font color = 'red'>A</font> <font color = 'red'>R</font>esearch <font color = 'red'>T</font>opic) is a science outreach program developed by the MSOE Center for BioMolecular Modeling. In this program, teams of high school students work with a local resarch lab to design and build a physical model of a protein that is being investigated by the lab. The goal of the SMART Team program is to introduce students to the real world of scince --- as it exists in a local research lab. The development of this program was supported by grants from the NIH-NCRR SEPA program (Science Education Partnership Award) and an HHMI Precollege Science Education Award. For more information about this program, visit the CBM web site at [http://www.rpc.msoe.edu/cbm www.rpc.msoe.edu/cbm] .

Elizaveta Sergeeva at 11:25, 7 February 2009

2009-02-07T11:25:28Z

← Older revision		Revision as of 11:25, 7 February 2009
Line 28:		Line 28:

	==<font color = 'blue'>Cell Signaling and Cell Movement</font>==		==<font color = 'blue'>Cell Signaling and Cell Movement</font>==
			[[Image:Filopodia.jpg\|left\|250px]]

	Cell signaling is how cells transmit information from the outside environment to inside the cell as well as how cells propagate messages within the cell. Transmembrane receptors at the cell surface detect environmental changes and pass the information on to intracellular signaling proteins. Proteins that make up signaling pathways pass along messages by interacting with each other.		Cell signaling is how cells transmit information from the outside environment to inside the cell as well as how cells propagate messages within the cell. Transmembrane receptors at the cell surface detect environmental changes and pass the information on to intracellular signaling proteins. Proteins that make up signaling pathways pass along messages by interacting with each other.
Line 43:		Line 44:

	='''<font color = 'black'>Cdc42: The GTPase</font>'''=		='''<font color = 'black'>Cdc42: The GTPase</font>'''=

			[[Image:GDP to GTP.jpg\|right\|250px]]

	Like other Rho GTPases, <scene name='SMART_Lincoln_2009/Cdc42_and_gdp/1'>Cdc42</scene> can exist in either the “Off” or “On” state. A guanine diphosphate (GDP) in the nucleotide-binding pocket indicates the “Off” state, and a guanine triphosphate (GTP) indicates the “On” state. _e activation from the “Off” state to the “On” state is catalyzed by a guanine-nucleotide exchange factor (GEF). Thee hydrolysis of GTP, which turns the GTPase off, is catalyzed by a GTPase activating protein called a GAP.		Like other Rho GTPases, <scene name='SMART_Lincoln_2009/Cdc42_and_gdp/1'>Cdc42</scene> can exist in either the “Off” or “On” state. A guanine diphosphate (GDP) in the nucleotide-binding pocket indicates the “Off” state, and a guanine triphosphate (GTP) indicates the “On” state. _e activation from the “Off” state to the “On” state is catalyzed by a guanine-nucleotide exchange factor (GEF). Thee hydrolysis of GTP, which turns the GTPase off, is catalyzed by a GTPase activating protein called a GAP.
Line 57:		Line 60:

	='''<font color = 'black'>How Intersectin Activates Cdc42</font>'''=		='''<font color = 'black'>How Intersectin Activates Cdc42</font>'''=

	~~<applet load='2rh1.pdb' size='350' frame='true' align='left' scene='SMART_Lincoln_2009/Complex_intersectin_and_cdc42/1'/>~~

	~~<scene name='SMART_Lincoln_2009/Cdc42_and_gdp/1'>Cdc42</scene>~~

	<scene name='SMART_Lincoln_2009/Complex_intersectin_and_cdc42/1'>Cdc42/Intersectin Complex</scene>		<scene name='SMART_Lincoln_2009/Complex_intersectin_and_cdc42/1'>Cdc42/Intersectin Complex</scene>
	The orientation of Alanine 59 is the highlight of Cdc42 activation by Intersectin. Alanine 59 causes the displacement of the Mg++ ion which in turn releases GDP from Cdc42’s binding pocket. Cdc42 is then able to accept a new nucleotide, specifically GTP, to become activated.		The orientation of Alanine 59 is the highlight of Cdc42 activation by Intersectin. Alanine 59 causes the displacement of the Mg++ ion which in turn releases GDP from Cdc42’s binding pocket. Cdc42 is then able to accept a new nucleotide, specifically GTP, to become activated.

	Cdc42 (yellow) is off when GDP is in its binding pocket. Mg++ is shown in magenta, Alanine 59 in green, Switch 1 in light gold, and Switch 2 in dark orange. Brown depicts the residues interacting with GDP (Lys16 and Cys18).		<applet load='2rh1.pdb' size='350' frame='true' align='left' scene='SMART_Lincoln_2009/Complex_intersectin_and_cdc42/1'/>

			-- <scene name='SMART_Lincoln_2009/Cdc42_and_gdp/1'>Cdc42</scene> (yellow) is off when GDP is in its binding pocket. Mg++ is shown in magenta, Alanine 59 in green, Switch 1 in light gold, and Switch 2 in dark orange. Brown depicts the residues interacting with GDP (Lys16 and Cys18).

	Intersectin (blue) binds to Cdc42, and its DH domain interacts with the GTPase.		-- <scene name='SMART_Lincoln_2009/Complex_intersectin_and_cdc42/1'>Cdc42/Intersectin Complex</scene>Intersectin (blue) binds to Cdc42, and its DH domain interacts with the GTPase.

	Thee interaction causes conformational changes in Switch 1 and Switch 2 of Cdc42. _r35 hydrogen bonds to a residue (Glu1244) of the DH domain of Intersectin. Most important is the noticeable change in the orientation of residue 59 (Ala59). Its sidechain flips into the magnesium-binding pocket, causing the release of the Mg++ ion and in turn the release of GDP from Cdc42.		-- Thee interaction causes conformational changes in Switch 1 and Switch 2 of Cdc42. _r35 hydrogen bonds to a residue (Glu1244) of the DH domain of Intersectin. Most important is the noticeable change in the orientation of residue 59 (Ala59). Its sidechain flips into the magnesium-binding pocket, causing the release of the Mg++ ion and in turn the release of GDP from Cdc42.

	Mg++ and GDP fall off from Cdc42. the nucleotide-binding pocket of Cdc42 is now empty.		-- Mg++ and GDP fall off from Cdc42. the nucleotide-binding pocket of Cdc42 is now empty.

	*Hypothetical depiction - ~~not based on structure data.~~		-- Because the intracellular ratio of GTP to GDP is high, a GTP molecule (dark green) will float into the binding pocket of Cdc42 and activate it.
	Because the intracellular ratio of GTP to GDP is high, a GTP molecule (dark green) will float into the binding pocket of Cdc42 and activate it.

Elizaveta Sergeeva: Cdc42 with GDP

2009-02-07T10:45:27Z

Cdc42 with GDP

@@ Line 44: / Line 44: @@
 ='''<font color = 'black'>Cdc42: The GTPase</font>'''=
-Like other Rho GTPases, Cdc42 can exist in either the “Off” or “On” state. A guanine diphosphate (GDP) in the nucleotide-binding pocket indicates the “Off” state, and a guanine triphosphate (GTP) indicates the “On” state. _e activation from the “Off” state to the “On” state is catalyzed by a guanine-nucleotide exchange factor (GEF). Thee hydrolysis of GTP, which turns the GTPase off, is catalyzed by a GTPase activating protein called a GAP.
+Like other Rho GTPases, <scene name='SMART_Lincoln_2009/Cdc42_and_gdp/1'>Cdc42</scene> can exist in either the “Off” or “On” state. A guanine diphosphate (GDP) in the nucleotide-binding pocket indicates the “Off” state, and a guanine triphosphate (GTP) indicates the “On” state. _e activation from the “Off” state to the “On” state is catalyzed by a guanine-nucleotide exchange factor (GEF). Thee hydrolysis of GTP, which turns the GTPase off, is catalyzed by a GTPase activating protein called a GAP.
 In addition to binding to a nucleotide (GDP or GTP), Cdc42 is usually found to be bound to a magnesium ion (Mg++), shown in magenta. The Mg++ sits near the nucleotide-binding pocket and helps to stabilize the Cdc42-nucleotide interaction.
@@ Line 58: / Line 58: @@
 ='''<font color = 'black'>How Intersectin Activates Cdc42</font>'''=
-<applet load='2rh1.pdb' size='400' frame='true' align='left' caption='Madison West SMART Team Model - β2-Adrenergic Receptor' scene='Hoelzer_Sandbox/Building_our_model/8'/>
+<applet load='2rh1.pdb' size='350' frame='true'  align='left' scene='SMART_Lincoln_2009/Complex_intersectin_and_cdc42/1'/>
-Cdc42/Intersectin Complex
+<scene name='SMART_Lincoln_2009/Cdc42_and_gdp/1'>Cdc42</scene>
 The orientation of Alanine 59 is the highlight of Cdc42 activation by Intersectin. Alanine 59 causes the displacement of the Mg++ ion which in turn releases GDP from Cdc42’s binding pocket. Cdc42 is then able to accept a new nucleotide, specifically GTP, to become activated.
@@ Line 76: / Line 78: @@
 ==<font color = 'red'>MSOE Center for BioMolecular Modeling and SMART Teams</font>==
 [[Image:Center for BioMolecular Modeling Logo.jpg|left|200px]]

Elizaveta Sergeeva at 08:06, 7 February 2009

2009-02-07T08:06:57Z

@@ Line 1: / Line 1: @@
 ='''<font color = 'black'> Tangible Models of Cdc42 Interacting With Intersectin </font>'''=
-=='''<font color = 'red'>A Lincoln HS SMART Team Telling a Molecular Story</font><font color = 'black'> --- from the Madison West High School 2008 SMART Team</font>'''==
+=='''<font color = 'red'>A Lincoln HS SMART Team Telling a Molecular Story</font><font color = 'black'></font>'''==
 :Abraham Lincoln High School, San Francisco, California
@@ Line 14: / Line 14: @@