Nathan Roy

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' 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' size='250' frame='true' align='right' caption='FIGURE 4. Domain swapped CA CTD' />