Group:SMART:Tangible Models of Cdc42 Interacting With Intersectin: Difference between revisions
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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]] | [[Image:Lincoln Team 2008.JPG|left|360px]] | ||
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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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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 = '# | 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 = '# | 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 = '#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 = '#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. | |||
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==''<font color = 'black'>Animation: How Intersectin Activates Cdc42</font>''== | |||
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