Allosteric modulation of H-Ras GTPase: Difference between revisions
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H-Ras is 166 Amino Acids long with six beta sheets and six helices. One of the helix 2 is a 3/10 helix, unlike the rest of the helices. Also it contains a Calcium Acetate in the allosteric binding site that is located by the Loop 7 and Helix 3. The structure of Ras actually forms slightly different when it is and isn't bound to calcium acetate. The GTP molecule will then attach on the bottom of the protein inbetween the Switch I and Switch II region. The switch I and switch II regions change conformation between their active and inactive state. This change in conformation of the switch regions helps other proteins determine whether the Ras protein is active or inactive. During the inactive stage Ras is bound to GDP and in the active stage it is bound to GTP. The effector protein Raf will bind to Ras protein when Ras is bound to GTP allowing it to help in the MAPK cascade. | H-Ras is 166 Amino Acids long with six beta sheets and six helices. One of the helix 2 is a 3/10 helix, unlike the rest of the helices. Also it contains a Calcium Acetate in the allosteric binding site that is located by the Loop 7 and Helix 3. The structure of Ras actually forms slightly different when it is and isn't bound to calcium acetate. The GTP molecule will then attach on the bottom of the protein inbetween the Switch I and Switch II region. The switch I and switch II regions change conformation between their active and inactive state. This change in conformation of the switch regions helps other proteins determine whether the Ras protein is active or inactive. During the inactive stage Ras is bound to GDP and in the active stage it is bound to GTP. The effector protein Raf will bind to Ras protein when Ras is bound to GTP allowing it to help in the MAPK cascade. | ||
Calcium acetate plays an important role in the activation of Ras protein. When it is bound to Ras protein, it will cause the Loop 7 and Helix 3 to shift and bend towards it. This will change the conformation of the entire protein and more importantly it will open up switch I and switch II allowing the γ-phosphate of GTP to hydrogen bond with Q61, T35 and Y32 residues through a water molecule. Add more about binding of calcium acetate and how it bends the loop 7 and helix 3 to allow switch I and switch II to bind to the GTP molecule [[Image:Ras calcium acetate and gppNHp2.jpg|thumb|400px|center|Calcium Acetate/Loop 7/Helix 3/GppNHp]] [[Image:Tileshop.jpeg|thumb|400px|right|Allosteric modulation of calcium acetate on Ras protein]] [[Image:Active and inactive.jpg|thumb| | Calcium acetate plays an important role in the activation of Ras protein. When it is bound to Ras protein, it will cause the Loop 7 and Helix 3 to shift and bend towards it. This will change the conformation of the entire protein and more importantly it will open up switch I and switch II allowing the γ-phosphate of GTP to hydrogen bond with Q61, T35 and Y32 residues through a water molecule. Add more about binding of calcium acetate and how it bends the loop 7 and helix 3 to allow switch I and switch II to bind to the GTP molecule [[Image:Ras calcium acetate and gppNHp2.jpg|thumb|400px|center|Calcium Acetate/Loop 7/Helix 3/GppNHp]] [[Image:Tileshop.jpeg|thumb|400px|right|Allosteric modulation of calcium acetate on Ras protein]] [[Image:Active and inactive.jpg|thumb|600px|left|Active and Inactive Ras protein]] [[Image:GTP binding real.jpeg|thumb|600px|left|γ-phosphate binding to Q61, T35 and Y32]] | ||
== Mutations and Cancer == | == Mutations and Cancer == | ||
