Group:SMART:Tangible Models of Cdc42 Interacting With Intersectin: Difference between revisions
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Cdc42 with GDP |
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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]] | |||
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 = '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. | ||
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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> | <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. | ||
-- 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. | |||
