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| | ==NMR Structure Determined for MLV NC Complex with RNA Sequence UAUCUG== | | ==NMR Structure Determined for MLV NC Complex with RNA Sequence UAUCUG== |
| - | <StructureSection load='1wwg' size='340' side='right'caption='[[1wwg]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='1wwg' size='340' side='right'caption='[[1wwg]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1wwg]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mlvmo Mlvmo]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WWG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1WWG FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1wwg]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Moloney_murine_leukemia_virus Moloney murine leukemia virus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WWG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1WWG FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1wwd|1wwd]], [[1wwe|1wwe]], [[1wwf|1wwf]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1wwg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wwg OCA], [https://pdbe.org/1wwg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1wwg RCSB], [https://www.ebi.ac.uk/pdbsum/1wwg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1wwg ProSAT]</span></td></tr> | | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1wwg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wwg OCA], [https://pdbe.org/1wwg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1wwg RCSB], [https://www.ebi.ac.uk/pdbsum/1wwg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1wwg ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/GAG_MLVMS GAG_MLVMS]] Gag polyprotein plays a role in budding and is processed by the viral protease during virion maturation outside the cell. During budding, it recruits, in a PPXY-dependent or independent manner, Nedd4-like ubiquitin ligases that conjugate ubiquitin molecules to Gag, or to Gag binding host factors. Interaction with HECT ubiquitin ligases probably link the viral protein to the host ESCRT pathway and facilitate release.<ref>PMID:19864377</ref> Matrix protein p15 targets Gag and gag-pol polyproteins to the plasma membrane via a multipartite membrane binding signal, that includes its myristoylated N-terminus. Also mediates nuclear localization of the preintegration complex (By similarity).<ref>PMID:19864377</ref> Capsid protein p30 forms the spherical core of the virion that encapsulates the genomic RNA-nucleocapsid complex (By similarity).<ref>PMID:19864377</ref> Nucleocapsid protein p10 is involved in the packaging and encapsidation of two copies of the genome. Binds with high affinity to conserved UCUG elements within the packaging signal, located near the 5'-end of the genome. This binding is dependent on genome dimerization.<ref>PMID:19864377</ref>
| + | [https://www.uniprot.org/uniprot/GAG_MLVMS GAG_MLVMS] Gag polyprotein plays a role in budding and is processed by the viral protease during virion maturation outside the cell. During budding, it recruits, in a PPXY-dependent or independent manner, Nedd4-like ubiquitin ligases that conjugate ubiquitin molecules to Gag, or to Gag binding host factors. Interaction with HECT ubiquitin ligases probably link the viral protein to the host ESCRT pathway and facilitate release.<ref>PMID:19864377</ref> Matrix protein p15 targets Gag and gag-pol polyproteins to the plasma membrane via a multipartite membrane binding signal, that includes its myristoylated N-terminus. Also mediates nuclear localization of the preintegration complex (By similarity).<ref>PMID:19864377</ref> Capsid protein p30 forms the spherical core of the virion that encapsulates the genomic RNA-nucleocapsid complex (By similarity).<ref>PMID:19864377</ref> Nucleocapsid protein p10 is involved in the packaging and encapsidation of two copies of the genome. Binds with high affinity to conserved UCUG elements within the packaging signal, located near the 5'-end of the genome. This binding is dependent on genome dimerization.<ref>PMID:19864377</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Mlvmo]] | + | [[Category: Moloney murine leukemia virus]] |
| - | [[Category: Dey, A]] | + | [[Category: Dey A]] |
| - | [[Category: Smalls-Mantey, A]] | + | [[Category: Smalls-Mantey A]] |
| - | [[Category: Summers, M F]] | + | [[Category: Summers MF]] |
| - | [[Category: York, D]] | + | [[Category: York D]] |
| - | [[Category: Hydrophobic guanosine binding pocket]]
| + | |
| - | [[Category: Viral protein-rna complex]]
| + | |
| Structural highlights
Function
GAG_MLVMS Gag polyprotein plays a role in budding and is processed by the viral protease during virion maturation outside the cell. During budding, it recruits, in a PPXY-dependent or independent manner, Nedd4-like ubiquitin ligases that conjugate ubiquitin molecules to Gag, or to Gag binding host factors. Interaction with HECT ubiquitin ligases probably link the viral protein to the host ESCRT pathway and facilitate release.[1] Matrix protein p15 targets Gag and gag-pol polyproteins to the plasma membrane via a multipartite membrane binding signal, that includes its myristoylated N-terminus. Also mediates nuclear localization of the preintegration complex (By similarity).[2] Capsid protein p30 forms the spherical core of the virion that encapsulates the genomic RNA-nucleocapsid complex (By similarity).[3] Nucleocapsid protein p10 is involved in the packaging and encapsidation of two copies of the genome. Binds with high affinity to conserved UCUG elements within the packaging signal, located near the 5'-end of the genome. This binding is dependent on genome dimerization.[4]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
All retroviruses package two copies of their genomes during virus assembly, both of which are required for strand transfer-mediated recombination during reverse transcription. Genome packaging is mediated by interactions between the nucleocapsid (NC) domains of assembling Gag polyproteins and an RNA packaging signal, located near the 5' end of the genome, called Psi. We recently discovered that the NC protein of the Moloney murine leukemia virus (MLV) can bind with high affinity to conserved UCUG elements within the MLV packaging signal [D'Souza, V., and Summers, M. F. (2004) Nature 431, 586-590]. Selective binding to dimeric RNA is regulated by a conformational RNA switch, in which the UCUG elements are sequestered by base pairing in the monomeric RNA and do not bind NC, but become exposed for NC binding upon dimerization. Dimerization-dependent structural changes occur in other regions of the Psi-site, exposing guanosine-containing segments that might also bind NC. Here we demonstrate that short RNAs containing three such sequences, ACAG, UUUG, and UCCG, can bind NC with significant affinity (K(d) = 94-315 nM). Titration experiments with oligoribonucleotides of varying lengths and compositions, combined with NMR-based structural studies, reveal that binding is strictly dependent on the presence of an unpaired guanosine, and that relative binding affinities can vary by more than 1 order of magnitude depending on the nature of the three upstream nucleotides. Binding is enhanced in short RNAs containing terminal phosphates, indicating that electrostatic interactions contribute significantly to binding. Our findings extend a previously published model for genome recognition, in which the NC domains of assembling Gag molecules interact with multiple X(i-3)-X(i-2)-X(i-1)-G(i) elements (X is a variable nucleotide) that appear to be preferentially exposed in the dimeric RNA.
Composition and sequence-dependent binding of RNA to the nucleocapsid protein of Moloney murine leukemia virus.,Dey A, York D, Smalls-Mantey A, Summers MF Biochemistry. 2005 Mar 15;44(10):3735-44. PMID:15751950[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Jadwin JA, Rudd V, Sette P, Challa S, Bouamr F. Late domain-independent rescue of a release-deficient Moloney murine leukemia virus by the ubiquitin ligase itch. J Virol. 2010 Jan;84(2):704-15. doi: 10.1128/JVI.01319-09. Epub 2009 Oct 28. PMID:19864377 doi:http://dx.doi.org/10.1128/JVI.01319-09
- ↑ Jadwin JA, Rudd V, Sette P, Challa S, Bouamr F. Late domain-independent rescue of a release-deficient Moloney murine leukemia virus by the ubiquitin ligase itch. J Virol. 2010 Jan;84(2):704-15. doi: 10.1128/JVI.01319-09. Epub 2009 Oct 28. PMID:19864377 doi:http://dx.doi.org/10.1128/JVI.01319-09
- ↑ Jadwin JA, Rudd V, Sette P, Challa S, Bouamr F. Late domain-independent rescue of a release-deficient Moloney murine leukemia virus by the ubiquitin ligase itch. J Virol. 2010 Jan;84(2):704-15. doi: 10.1128/JVI.01319-09. Epub 2009 Oct 28. PMID:19864377 doi:http://dx.doi.org/10.1128/JVI.01319-09
- ↑ Jadwin JA, Rudd V, Sette P, Challa S, Bouamr F. Late domain-independent rescue of a release-deficient Moloney murine leukemia virus by the ubiquitin ligase itch. J Virol. 2010 Jan;84(2):704-15. doi: 10.1128/JVI.01319-09. Epub 2009 Oct 28. PMID:19864377 doi:http://dx.doi.org/10.1128/JVI.01319-09
- ↑ Dey A, York D, Smalls-Mantey A, Summers MF. Composition and sequence-dependent binding of RNA to the nucleocapsid protein of Moloney murine leukemia virus. Biochemistry. 2005 Mar 15;44(10):3735-44. PMID:15751950 doi:http://dx.doi.org/10.1021/bi047639q
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