2vqz: Difference between revisions

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==Structure of the cap-binding domain of influenza virus polymerase subunit PB2 with bound m7GTP==
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<StructureSection load='2vqz' size='340' side='right'caption='[[2vqz]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2vqz]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Influenza_A_virus Influenza A virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VQZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VQZ FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MGT:7N-METHYL-8-HYDROGUANOSINE-5-TRIPHOSPHATE'>MGT</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
{{STRUCTURE_2vqz|  PDB=2vqz  |  SCENE=  }}
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2vqz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vqz OCA], [https://pdbe.org/2vqz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vqz RCSB], [https://www.ebi.ac.uk/pdbsum/2vqz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vqz ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PB2_I75A3 PB2_I75A3] Involved in transcription initiation and cap-stealing mechanism, in which cellular capped pre-mRNA are used to generate primers for viral transcription. Binds the cap of the target pre-RNA which is subsequently cleaved by PB1. May play a role in genome replication (By similarity).
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Influenza virus mRNAs are synthesized by the trimeric viral polymerase using short capped primers obtained by a 'cap-snatching' mechanism. The polymerase PB2 subunit binds the 5' cap of host pre-mRNAs, which are cleaved after 10-13 nucleotides by the PB1 subunit. Using a library-screening method, we identified an independently folded domain of PB2 that has specific cap binding activity. The X-ray structure of the domain with bound cap analog m(7)GTP at 2.3-A resolution reveals a previously unknown fold and a mode of ligand binding that is similar to, but distinct from, other cap binding proteins. Binding and functional studies with point mutants confirm that the identified site is essential for cap binding in vitro and cap-dependent transcription in vivo by the trimeric polymerase complex. These findings clarify the nature of the cap binding site in PB2 and will allow efficient structure-based design of new anti-influenza compounds inhibiting viral transcription.


'''STRUCTURE OF THE CAP-BINDING DOMAIN OF INFLUENZA VIRUS POLYMERASE SUBUNIT PB2 WITH BOUND M7GTP'''
The structural basis for cap binding by influenza virus polymerase subunit PB2.,Guilligay D, Tarendeau F, Resa-Infante P, Coloma R, Crepin T, Sehr P, Lewis J, Ruigrok RW, Ortin J, Hart DJ, Cusack S Nat Struct Mol Biol. 2008 May;15(5):500-6. Epub 2008 May 4. PMID:18454157<ref>PMID:18454157</ref>


From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2vqz" style="background-color:#fffaf0;"></div>


==Overview==
==See Also==
The trimeric influenza virus polymerase, comprising subunits PA, PB1 and PB2, is responsible for transcription and replication of the segmented viral RNA genome. Using a novel library-based screening technique called expression of soluble proteins by random incremental truncation (ESPRIT), we identified an independently folded C-terminal domain from PB2 and determined its solution structure by NMR. Using green fluorescent protein fusions, we show that both the domain and the full-length PB2 subunit are efficiently imported into the nucleus dependent on a previously overlooked bipartite nuclear localization sequence (NLS). The crystal structure of the domain complexed with human importin alpha5 shows how the last 20 residues unfold to permit binding to the import factor. The domain contains three surface residues implicated in adaptation from avian to mammalian hosts. One of these tethers the NLS-containing peptide to the core of the domain in the unbound state.
*[[RNA polymerase 3D structures|RNA polymerase 3D structures]]
 
== References ==
==About this Structure==
<references/>
2VQZ is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Influenza_a_virus Influenza a virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VQZ OCA].
__TOC__
 
</StructureSection>
==Reference==
[[Category: Influenza A virus]]
Structure and nuclear import function of the C-terminal domain of influenza virus polymerase PB2 subunit., Tarendeau F, Boudet J, Guilligay D, Mas PJ, Bougault CM, Boulo S, Baudin F, Ruigrok RW, Daigle N, Ellenberg J, Cusack S, Simorre JP, Hart DJ, Nat Struct Mol Biol. 2007 Mar;14(3):229-33. Epub 2007 Feb 25. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17310249 17310249]
[[Category: Large Structures]]
[[Category: Influenza a virus]]
[[Category: Coloma R]]
[[Category: Single protein]]
[[Category: Crepin T]]
[[Category: Coloma, R.]]
[[Category: Cusack S]]
[[Category: Crepin, T.]]
[[Category: Guilligay D]]
[[Category: Cusack, S.]]
[[Category: Hart DJ]]
[[Category: Guilligay, D.]]
[[Category: Lewis J]]
[[Category: Hart, D J.]]
[[Category: Ortin J]]
[[Category: Lewis, J.]]
[[Category: Resa-Infante P]]
[[Category: Ortin, J.]]
[[Category: Ruigrok RWH]]
[[Category: Resa-Infante, P.]]
[[Category: Sehr P]]
[[Category: Ruigrok, R W.H.]]
[[Category: Tarendeau F]]
[[Category: Sehr, P.]]
[[Category: Tarendeau, F.]]
[[Category: Cap-binding domain]]
[[Category: Influenza virus]]
[[Category: Pb2 subunit]]
[[Category: Rna-dependent rna polymerase]]
[[Category: Transcription]]
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