1osw
From Proteopedia
(New page: 200px<br /> <applet load="1osw" size="450" color="white" frame="true" align="right" spinBox="true" caption="1osw" /> '''The Stem of SL1 RNA in HIV-1: Structure and...) |
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'''The Stem of SL1 RNA in HIV-1: Structure and Nucleocapsid Protein Binding for a 1X3 Internal Loop'''<br /> | '''The Stem of SL1 RNA in HIV-1: Structure and Nucleocapsid Protein Binding for a 1X3 Internal Loop'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The 5'-leader of HIV-1 RNA controls many viral functions. Nucleocapsid | + | The 5'-leader of HIV-1 RNA controls many viral functions. Nucleocapsid (NC) domains of gag-precursor proteins select genomic RNA for packaging by binding several sites in the leader. One is likely to be a stem defect in SL1 that can adopt either a 1 x 3 internal loop, SL1i (including G247, A271, G272, G273) or a 1 x 1 internal loop (G247 x G273) near a two-base bulge (A269-G270). It is likely that these two conformations are both present and exchange readily. A 23mer RNA construct described here models SL1i and cannot slip into the alternate form. It forms a 1:1 complex with NCp7, which interacts most strongly at G247 and G272 (K(d) = 140 nM). This demonstrates that a linear G-X-G sequence is unnecessary for high-affinity binding. The NMR-based structure shows an easily broken G247:A271 base pair. G247 stacks on both of its immediate neighbors and A271 on its 5'-neighbor; G272 and G273 are partially ordered. A bend in the helix axis between the SL1 stems on either side of the internal loop is probable. An important step in maturation of the virus is the transition from an apical loop-loop interaction to a dimer involving intermolecular interactions along the full length of SL1. A bend in the stem may be important in relieving strain and ensuring that the strands do not become entangled during the transition. A stem defect with special affinity for NCp7 may accelerate the rate of the dimer transformation. This complex could become an important target for anti-HIV drug development, where a drug could exert its action near a high-energy intermediate on the pathway for maturation of the dimer. |
==About this Structure== | ==About this Structure== | ||
| - | 1OSW is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http:// | + | 1OSW is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OSW OCA]. |
==Reference== | ==Reference== | ||
Stem of SL1 RNA in HIV-1: structure and nucleocapsid protein binding for a 1 x 3 internal loop., Yuan Y, Kerwood DJ, Paoletti AC, Shubsda MF, Borer PN, Biochemistry. 2003 May 13;42(18):5259-69. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12731867 12731867] | Stem of SL1 RNA in HIV-1: structure and nucleocapsid protein binding for a 1 x 3 internal loop., Yuan Y, Kerwood DJ, Paoletti AC, Shubsda MF, Borer PN, Biochemistry. 2003 May 13;42(18):5259-69. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12731867 12731867] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Borer, P | + | [[Category: Borer, P N.]] |
| - | [[Category: Kerwood, D | + | [[Category: Kerwood, D J.]] |
| - | [[Category: Paoletti, A | + | [[Category: Paoletti, A C.]] |
| - | [[Category: Shubsda, M | + | [[Category: Shubsda, M F.]] |
[[Category: Yuan, Y.]] | [[Category: Yuan, Y.]] | ||
[[Category: rna]] | [[Category: rna]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:21:11 2008'' |
Revision as of 12:21, 21 February 2008
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The Stem of SL1 RNA in HIV-1: Structure and Nucleocapsid Protein Binding for a 1X3 Internal Loop
Overview
The 5'-leader of HIV-1 RNA controls many viral functions. Nucleocapsid (NC) domains of gag-precursor proteins select genomic RNA for packaging by binding several sites in the leader. One is likely to be a stem defect in SL1 that can adopt either a 1 x 3 internal loop, SL1i (including G247, A271, G272, G273) or a 1 x 1 internal loop (G247 x G273) near a two-base bulge (A269-G270). It is likely that these two conformations are both present and exchange readily. A 23mer RNA construct described here models SL1i and cannot slip into the alternate form. It forms a 1:1 complex with NCp7, which interacts most strongly at G247 and G272 (K(d) = 140 nM). This demonstrates that a linear G-X-G sequence is unnecessary for high-affinity binding. The NMR-based structure shows an easily broken G247:A271 base pair. G247 stacks on both of its immediate neighbors and A271 on its 5'-neighbor; G272 and G273 are partially ordered. A bend in the helix axis between the SL1 stems on either side of the internal loop is probable. An important step in maturation of the virus is the transition from an apical loop-loop interaction to a dimer involving intermolecular interactions along the full length of SL1. A bend in the stem may be important in relieving strain and ensuring that the strands do not become entangled during the transition. A stem defect with special affinity for NCp7 may accelerate the rate of the dimer transformation. This complex could become an important target for anti-HIV drug development, where a drug could exert its action near a high-energy intermediate on the pathway for maturation of the dimer.
About this Structure
1OSW is a Protein complex structure of sequences from [1]. Full crystallographic information is available from OCA.
Reference
Stem of SL1 RNA in HIV-1: structure and nucleocapsid protein binding for a 1 x 3 internal loop., Yuan Y, Kerwood DJ, Paoletti AC, Shubsda MF, Borer PN, Biochemistry. 2003 May 13;42(18):5259-69. PMID:12731867
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