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| | {{STRUCTURE_1wwd| PDB=1wwd | SCENE= }} | | {{STRUCTURE_1wwd| PDB=1wwd | SCENE= }} |
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| - | '''NMR structure determined for MLV NC complex with RNA sequence AACAGU'''
| + | ===NMR structure determined for MLV NC complex with RNA sequence AACAGU=== |
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| - | ==Overview==
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| - | 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.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_15751950}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 15751950 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_15751950}} |
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| | ==About this Structure== | | ==About this Structure== |
| - | 1WWD is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Moloney_murine_leukemia_virus Moloney murine leukemia virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WWD OCA]. | + | 1WWD is a [[Single protein]] structure of sequence from [http://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=1WWD OCA]. |
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| | ==Reference== | | ==Reference== |
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| | [[Category: York, D.]] | | [[Category: York, D.]] |
| | [[Category: Hydrophobic guanosine binding pocket]] | | [[Category: Hydrophobic guanosine binding pocket]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 14:13:30 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 07:54:27 2008'' |
Revision as of 04:54, 29 July 2008
Template:STRUCTURE 1wwd
NMR structure determined for MLV NC complex with RNA sequence AACAGU
Template:ABSTRACT PUBMED 15751950
About this Structure
1WWD is a Single protein structure of sequence from Moloney murine leukemia virus. Full experimental information is available from OCA.
Reference
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
Page seeded by OCA on Tue Jul 29 07:54:27 2008
