User:Nathan Roy: Difference between revisions

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When MA is not bound to PI(4,5)P2 (Figure 1), notice the alignment of helix 1, and more precisely, the orientation of Leu 8 and Glu 12(<scene name='User:Nathan_Roy/Unbound_residues/2'>Show Residues</scene>).<applet load='2H3Q_mono1.pdb' size='300' frame='true' align='left' caption='FIGURE 2. MA bound to PI(4,5)P2' /> In this PI(4,5)P2 unbound structure, the myristyl group is sequestered in the pocket of helix 1 created by Leu 8 and Glu 12. Upon binding of PI(4,5)P2 to the hydrophobic groove created by helix 2, a type 2 beta turn, and helix 5, a slight conformational switch occurs in helix 1 (Figure 2), causing a change in the alignment of Leu 8 and Glu 12,(<scene name='User:Nathan_Roy/Myr_out/2'>Show Residues</scene>) ejecting the myristyl group from it's sequestered state. This structural switch allows membrane anchoring to be directly coupled to proper membrane localization of Gag, and thus efficient particle release.

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Once Gag is localized to discreet sites on the plasma membrane, multimerization of Gag takes place quite quickly , driven by the CA domain, and more specifically our focus here, the C-terminal domain of CA (CTD). There are four helices that contribute to the interaction of CA CTD with it's partner. A side-by-side interaction has been proposed (Figure 3), but many believe the forces involved in the side-by-side model are not great enough to account for the organization and structural stability of assembled Gag. Also, helix 1 of the CA CTD contains a very conserved region of residues within many retroviruses called the MHR (major homology region). In the side-by-side model, the MHR is not responsible for the dimer organization, therefore a model of the CA CTD dimer in which the MHR is responsible for organization of the CA CTD dimers has been sought. ~~<applet load='1aum_dimer.pdb' size='250' frame='true' align='right' caption='FIGURE 3. Side-by-side structure of CA CTD' />~~ By making a single deletion of the Ala 177 residue (which lies in the loop between helix 1 and helix 2), the CA CTD domain adopts a domain-swapped conformation, in which the MHR of helix 1 is extended to contact helices 2,3, and 4 of the adjacent CA CTD domain (Figure 4). This domain swapping allows for a tighter binging of the CA CTD domains, and a stronger, and more rigid viral capsid. <applet load='2ont_dimer.pdb' size='250' frame='true' align='right' caption='FIGURE 4. Domain swapped CA CTD' />

Once Gag is localized to discreet sites on the plasma membrane, multimerization of Gag takes place quite quickly , driven by the CA domain, and more specifically our focus here, the C-terminal domain of CA (CTD). There are four helices that contribute to the interaction of CA CTD with it's partner. A side-by-side interaction has been proposed (Figure 3), but many believe the forces involved in the side-by-side model are not great enough to account for the organization and structural stability of assembled Gag. Also, helix 1 of the CA CTD contains a very conserved region of residues within many retroviruses called the MHR (major homology region). In the side-by-side model, the MHR is not responsible for the dimer organization, therefore a model of the CA CTD dimer in which the MHR is responsible for organization of the CA CTD dimers has been sought. By making a single deletion of the Ala 177 residue (which lies in the loop between helix 1 and helix 2), the CA CTD domain adopts a domain-swapped conformation, in which the MHR of helix 1 is extended to contact helices 2,3, and 4 of the adjacent CA CTD domain (Figure 4). This domain swapping allows for a tighter binging of the CA CTD domains, and a stronger, and more rigid viral capsid. <applet load='2ont_dimer.pdb' size='250' frame='true' align='right' caption='FIGURE 4. Domain swapped CA CTD' />

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 When MA is not bound to PI(4,5)P2 (Figure 1), notice the alignment of helix 1, and more precisely, the orientation of Leu 8 and Glu 12(<scene name='User:Nathan_Roy/Unbound_residues/2'>Show Residues</scene>).<applet load='2H3Q_mono1.pdb' size='300' frame='true' align='left' caption='FIGURE 2. MA bound to PI(4,5)P2' />  In this PI(4,5)P2 unbound structure, the myristyl group is sequestered in the pocket of helix 1 created by Leu 8 and Glu 12. Upon binding of PI(4,5)P2 to the hydrophobic groove created by helix 2, a type 2 beta turn, and helix 5, a slight conformational switch occurs in helix 1 (Figure 2), causing a change in the alignment of Leu 8 and Glu 12,(<scene name='User:Nathan_Roy/Myr_out/2'>Show Residues</scene>) ejecting the myristyl group from it's sequestered state. This structural switch allows membrane anchoring to be directly coupled to proper membrane localization of Gag, and thus efficient particle release.
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+<applet load='1aum_dimer.pdb' size='250' frame='true' align='right' caption='FIGURE 3. Side-by-side structure of CA CTD' />
-Once Gag is localized to discreet sites on the plasma membrane, multimerization of Gag takes place quite quickly , driven by the CA domain, and more specifically our focus here, the C-terminal domain of CA (CTD). There are four helices that contribute to the interaction of CA CTD with it's partner. A side-by-side interaction has been proposed (Figure 3), but many believe the forces involved in the side-by-side model are not great enough to account for the organization and structural stability of assembled Gag. Also, helix 1 of the CA CTD contains a very conserved region of residues within many retroviruses called the MHR (major homology region). In the side-by-side model, the MHR is not responsible for the dimer organization, therefore a model of the CA CTD dimer in which the MHR is responsible for organization of the CA CTD dimers has been sought. <applet load='1aum_dimer.pdb' size='250' frame='true' align='right' caption='FIGURE 3. Side-by-side structure of CA CTD' /> By making a single deletion of the Ala 177 residue (which lies in the loop between helix 1 and helix 2), the CA CTD domain adopts a domain-swapped conformation, in which the MHR of helix 1 is extended to contact helices 2,3, and 4 of the adjacent CA CTD domain (Figure 4). This domain swapping allows for a tighter binging of the CA CTD domains, and a stronger, and more rigid viral capsid. <applet load='2ont_dimer.pdb' size='250' frame='true' align='right' caption='FIGURE 4. Domain swapped CA CTD' />
+Once Gag is localized to discreet sites on the plasma membrane, multimerization of Gag takes place quite quickly , driven by the CA domain, and more specifically our focus here, the C-terminal domain of CA (CTD). There are four helices that contribute to the interaction of CA CTD with it's partner. A side-by-side interaction has been proposed (Figure 3), but many believe the forces involved in the side-by-side model are not great enough to account for the organization and structural stability of assembled Gag. Also, helix 1 of the CA CTD contains a very conserved region of residues within many retroviruses called the MHR (major homology region). In the side-by-side model, the MHR is not responsible for the dimer organization, therefore a model of the CA CTD dimer in which the MHR is responsible for organization of the CA CTD dimers has been sought.  By making a single deletion of the Ala 177 residue (which lies in the loop between helix 1 and helix 2), the CA CTD domain adopts a domain-swapped conformation, in which the MHR of helix 1 is extended to contact helices 2,3, and 4 of the adjacent CA CTD domain (Figure 4). This domain swapping allows for a tighter binging of the CA CTD domains, and a stronger, and more rigid viral capsid. <applet load='2ont_dimer.pdb' size='250' frame='true' align='right' caption='FIGURE 4. Domain swapped CA CTD' />