User:Nathan Roy: Difference between revisions
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As we have seen, Gag is responsible for correct targeting of viral assembly to discreet sites on the plasma membrane, and viral capsid structure assembly into organized virus particles. However, Gag is also responsible for packaging of the viral RNA into budding virions, and this function in executed by the NC domain. The 5' LTR of HIV-1 genomic RNA contains a recognition element called the psi element. All retroviruses contain some type of psi element in order to get specific packaging of viral genomic RNA within the budding particles, and in the case of HIV-1, the psi element is 120 bases, and contains 4 stem-loop structures. Although the psi element can be quite variable, the SL3 loop is highly conserved within HIV-1 strains. Figure 5 shows the NC domain of HIV-1 NL4-3 in complex with the SL3 loop of the viral psi element. | As we have seen, Gag is responsible for correct targeting of viral assembly to discreet sites on the plasma membrane, and viral capsid structure assembly into organized virus particles. However, Gag is also responsible for packaging of the viral RNA into budding virions, and this function in executed by the NC domain. The 5' LTR of HIV-1 genomic RNA contains a recognition element called the psi element. All retroviruses contain some type of psi element in order to get specific packaging of viral genomic RNA within the budding particles, and in the case of HIV-1, the psi element is 120 bases, and contains 4 stem-loop structures. Although the psi element can be quite variable, the SL3 loop is highly conserved within HIV-1 strains. Figure 5 shows the NC domain of HIV-1 NL4-3 in complex with the SL3 loop of the viral psi element. | ||
There are two zinc knuckle domains, with the zinc ion held by three Cys residues and a His(<scene name='User:Nathan_Roy/Zinc_knuckle/1'>Knuckle</scene>). Notice that guanine210 and guanine212 of the RNA interact with the F2 and F1 CCHC zinc knuckles respectively. In the F1 knuckle, G9 fits into a hydrophobic cleft formed by Val13, Phe16, Ile24, and Ala 25. G9 satisfies Watson-Crick hydrogen bonding by interacting with the NH groups from Phe16 and Ala25(<scene name='User:Nathan_Roy/F1_interaction/1'>Show residues</scene>), and also the CO group of Lys14 | There are two zinc knuckle domains, with the zinc ion held by three Cys residues and a His(<scene name='User:Nathan_Roy/Zinc_knuckle/1'>Knuckle</scene>). Notice that guanine210 and guanine212 of the RNA interact with the F2 and F1 CCHC zinc knuckles respectively. In the F1 knuckle, G9 fits into a hydrophobic cleft formed by Val13, Phe16, Ile24, and Ala 25. G9 satisfies Watson-Crick hydrogen bonding by interacting with the NH groups from Phe16 and Ala25(<scene name='User:Nathan_Roy/F1_interaction/1'>Show residues</scene>), and also the CO group of Lys14 | ||
(<scene name='User:Nathan_Roy/F1_interaction/2'>Show</scene>). G7 interacts much the same with the F2 knuckle by hydrogen bonding with the NH groups of Trp37 and Met46, while also hydrogen bonding with the CO group of Gly35. The adenine211 nucleotide forms a hydrogen bond with a highly conserved Arg32 residue(<scene name='User:Nathan_Roy/F1_interaction/3'>Show</scene>). Also, residues 3 thru 10 form a 3.10 helix, which nestles into the RNA major groove(<scene name='User:Nathan_Roy/3-10_helix/1'>Show helix</scene>). These interactions allow viral RNA to be specifically packaged into virions. Also of note, it has been shown that NC binding of viral RNA increases the ability of Gag to multimerize, thus providing another mechanism to couple functional virion assembly to Gag multimerization and | (<scene name='User:Nathan_Roy/F1_interaction/2'>Show</scene>). G7 interacts much the same with the F2 knuckle by hydrogen bonding with the NH groups of Trp37 and Met46, while also hydrogen bonding with the CO group of Gly35. The adenine211 nucleotide forms a hydrogen bond with a highly conserved Arg32 residue(<scene name='User:Nathan_Roy/F1_interaction/3'>Show</scene>). Also, residues 3 thru 10 form a 3.10 helix, which nestles into the RNA major groove(<scene name='User:Nathan_Roy/3-10_helix/1'>Show helix</scene>). These interactions allow viral RNA to be specifically packaged into virions. Also of note, it has been shown that NC binding of viral RNA increases the ability of Gag to multimerize, thus providing another mechanism to couple functional virion assembly to Gag multimerization and viral budding. | ||
==Reference== | |||
<ref group="xtra">PMID:9430589</ref><references group="xtra"/> | |||
<ref group="xtra">PMID:15016358</ref><references group="xtra"/> | |||
<ref group="xtra">PMID:15016358</ref><references group="xtra"/> | |||
<ref group="xtra">PMID:15016358</ref><references group="xtra"/> | |||
<ref group="xtra">PMID:15016358</ref><references group="xtra"/> | |||
<ref group="xtra">PMID:15016358</ref><references group="xtra"/> | |||