Sandbox 154: Difference between revisions
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=== Nucleotide-State-Dependent Conformational Changes === | === Nucleotide-State-Dependent Conformational Changes === | ||
The state of the bound phosphorylated nucleotide affects what conformation the F-actin monomer undertakes. The presence of a gamma-phosphate in the active site causes the rotation of a Ser14 residue. This change leads to HIC73 (4-methyl histidine) becoming shifted, which alters the F-actin active site and causes a conformational change in the D-loop. The HIC73 is located in the sensor loop, or the "switch" for linking changes in bound nucleotide to conformational changes<ref name="Graceffa"/>. In ATP-actin and ADP-P<sub>i</sub>-actin, the D-loop is unstructured. In the ADP-bound form of F-actin, an alpha helix is commonly apparent in the D-loop of the monomer<ref name="Pfaendtner"/><ref name="Graceffa"/>. Although the alpha-helix is not observed in this Oda model of F-actin, it is acknowkledged by Oda et. al that the experimental results could have lead to an extended alpha-helix in the model<ref name="oda"/>. | The state of the bound phosphorylated nucleotide affects what conformation the F-actin monomer undertakes. The presence of a gamma-phosphate in the active site causes the rotation of a Ser14 residue. This change leads to HIC73 (4-methyl histidine) becoming shifted, which alters the F-actin active site and causes a conformational change in the D-loop. The HIC73 is located in the sensor loop, or the "switch" for linking changes in bound nucleotide to conformational changes<ref name="Graceffa"/>. In ATP-actin and ADP-P<sub>i</sub>-actin, the D-loop is unstructured. In the ADP-bound form of F-actin, an alpha helix is commonly apparent in the D-loop of the monomer<ref name="Pfaendtner"/><ref name="Graceffa"/>. | ||
Although the alpha-helix is not observed in this Oda model of F-actin and is not seen in some other F-actin studies<ref name=”oda”/><ref name=”dalhaimer”/>, it is acknowkledged by Oda et. al that the experimental results could have lead to an extended alpha-helix in the model<ref name="oda"/>. | |||
==== Domains ==== | ==== Domains ==== | ||
<applet load='2zwh' size='275' color='black' frame='true' align='right' caption='Filamentous Actin (F-actin)' scene='Sandbox_154/2zwh_black_domains/1'/> | <applet load='2zwh' size='275' color='black' frame='true' align='right' caption='Filamentous Actin (F-actin)' scene='Sandbox_154/2zwh_black_domains/1'/> | ||
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==== Stability ==== | ==== Stability ==== | ||
The flattened folded form of F-actin requires different stabilization mechanisms than the free monomeric G-actin form. Stability of the F-actin complex is achieved by a series of <scene name='Sandbox_154/2zwh_saltbridge/1'>salt bridge</scene> formations involving arginine 206, 183, 177 (purple); glutamate 72(blue), aspartate 187(green), 179 and 4-methyl histidine 73(yellow). Additional stability is believed to arise from a break in the interaction between residues <scene name='Sandbox_154/2zwh_leu_val/2'>108-111 and Val165 and Ile175</scene> in the same half of their respective domains to a new interaction between <scene name='Sandbox_154/2zwh_leu_thr/2'>Leu110 and Thr194</scene> where a much greater distance is observed between them<ref name="oda" />. | The flattened folded form of F-actin requires different stabilization mechanisms than the free monomeric G-actin form. Stability of the F-actin complex is achieved by a series of <scene name='Sandbox_154/2zwh_saltbridge/1'>salt bridge</scene> formations involving arginine 206, 183, 177 (purple); glutamate 72(blue), aspartate 187(green), 179 and 4-methyl histidine 73(yellow). Additional stability is believed to arise from a break in the interaction between residues <scene name='Sandbox_154/2zwh_leu_val/2'>108-111 and Val165 and Ile175</scene> in the same half of their respective domains to a new interaction between <scene name='Sandbox_154/2zwh_leu_thr/2'>Leu110 and Thr194</scene> where a much greater distance is observed between them<ref name="oda" />. | ||
Once the P<sub>i</sub> is released, a conformational change on the D-loop results in the “softening” of the F-actin filament. That is, it makes the ADP-actin monomer more unstable and makes it more susceptible to cleavage <ref name=”Pfaedtner2”>PMID: 19931282</ref> | |||
==== Active Site ==== | ==== Active Site ==== | ||
