2im3: Difference between revisions

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-{{Seed}}
-[[Image:2im3.png|left|200px]]
-<!--
+==Crystal structure of poliovirus polymerase complexed with UTP and Mn2+==
-The line below this paragraph, containing "STRUCTURE_2im3", creates the "Structure Box" on the page.
+<StructureSection load='2im3' size='340' side='right'caption='[[2im3]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[2im3]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_poliovirus_1_Mahoney Human poliovirus 1 Mahoney]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2IM3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2IM3 FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACY:ACETIC+ACID'>ACY</scene>, <scene name='pdbligand=CAS:S-(DIMETHYLARSENIC)CYSTEINE'>CAS</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=UTP:URIDINE+5-TRIPHOSPHATE'>UTP</scene></td></tr>
-{{STRUCTURE_2im3|  PDB=2im3  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2im3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2im3 OCA], [https://pdbe.org/2im3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2im3 RCSB], [https://www.ebi.ac.uk/pdbsum/2im3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2im3 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/POLG_POL1M POLG_POL1M] Capsid proteins VP1, VP2, VP3 and VP4 form a closed capsid enclosing the viral positive strand RNA genome. VP4 lies on the inner surface of the protein shell formed by VP1, VP2 and VP3. All the three latter proteins contain a beta-sheet structure called beta-barrel jelly roll. Together they form an icosahedral capsid (T=3) composed of 60 copies of each VP1, VP2, and VP3, with a diameter of approximately 300 Angstroms. VP1 is situated at the 12 fivefold axes, whereas VP2 and VP3 are located at the quasi-sixfold axes. The interaction of five VP1 proteins in the fivefold axes results in a prominent protusion extending to about 25 Angstroms from the capsid shell. The resulting structure appears as a steep plateau encircled by a valley or cleft. This depression also termed canyon is the receptor binding site. The capsid interacts with human PVR at this site to provide virion attachment to target cell. This attachment induces virion internalization predominantly through clathrin- and caveolin-independent endocytosis in Hela cells and through caveolin-mediated endocytosis in brain microvascular endothelial cells. VP4 and VP1 subsequently undergo conformational changes leading to the formation of a pore in the endosomal membrane, thereby delivering the viral genome into the cytoplasm.<ref>PMID:9755863</ref> <ref>PMID:15919927</ref> <ref>PMID:18191571</ref>   VP0 precursor is a component of immature procapsids (By similarity).<ref>PMID:9755863</ref> <ref>PMID:15919927</ref> <ref>PMID:18191571</ref>   Protein 2A is a cysteine protease that is responsible for the cleavage between the P1 and P2 regions. It cleaves the host translation initiation factor EIF4G1, in order to shut down the capped cellular mRNA transcription.<ref>PMID:9755863</ref> <ref>PMID:15919927</ref> <ref>PMID:18191571</ref>   Protein 2B affects membrane integrity and cause an increase in membrane permeability (By similarity).<ref>PMID:9755863</ref> <ref>PMID:15919927</ref> <ref>PMID:18191571</ref>   Protein 2C associates with and induces structural rearrangements of intracellular membranes. It displays RNA-binding, nucleotide binding and NTPase activities.<ref>PMID:9755863</ref> <ref>PMID:15919927</ref> <ref>PMID:18191571</ref>   Protein 3A, via its hydrophobic domain, serves as membrane anchor. It also inhibits endoplasmic reticulum-to-Golgi transport (By similarity).<ref>PMID:9755863</ref> <ref>PMID:15919927</ref> <ref>PMID:18191571</ref>   Protein 3C is a cysteine protease that generates mature viral proteins from the precursor polyprotein. In addition to its proteolytic activity, it binds to viral RNA, and thus influences viral genome replication. RNA and substrate bind co-operatively to the protease (By similarity).<ref>PMID:9755863</ref> <ref>PMID:15919927</ref> <ref>PMID:18191571</ref>   RNA-directed RNA polymerase 3D-POL replicates genomic and antigenomic RNA by recognizing replications specific signals (By similarity).<ref>PMID:9755863</ref> <ref>PMID:15919927</ref> <ref>PMID:18191571</ref>
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/im/2im3_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2im3 ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The viral RNA-dependent RNA polymerases show a conserved structure where the fingers domain interacts with the top of the thumb domain to create a tunnel through which nucleotide triphosphates reach the active site. We have solved the crystal structures of poliovirus polymerase (3D(pol)) in complex with all four NTPs, showing that they all bind in a common pre-insertion site where the phosphate groups are not yet positioned over the active site. The NTPs interact with both the fingers and palm domains, forming bridging interactions that explain the increased thermal stability of 3D(pol) in the presence of NTPs. We have also examined the importance of the fingers-thumb domain interaction for the function and structural stability of 3D(pol). Results from thermal denaturation experiments using circular dichroism and 2-anilino-6-napthaline-sulfonate (ANS) fluorescence show that 3D(pol) has a melting temperature of only approximately 40 degrees C. NTP binding stabilizes the protein and increases the melting by 5-6 degrees C while mutations in the fingers-thumb domain interface destabilize the protein and reduce the melting point by as much as 6 degrees C. In particular, the burial of Phe30 and Phe34 from the tip of the index finger into a pocket at the top of the thumb and the presence of Trp403 on the thumb domain are key interactions required to maintain the structural integrity of the polymerase. The data suggest the fingers domain has significant conformational flexibility and exists in a highly dynamic molten globule state at physiological temperature. The role of the enclosed active site motif as a structural scaffold for constraining the fingers domain and accommodating conformational changes in 3D(pol) and other viral polymerases during the catalytic cycle is discussed.
-===Crystal structure of poliovirus polymerase complexed with UTP and Mn2+===
+Stabilization of poliovirus polymerase by NTP binding and fingers-thumb interactions.,Thompson AA, Albertini RA, Peersen OB J Mol Biol. 2007 Mar 9;366(5):1459-74. Epub 2006 Dec 1. PMID:17223130<ref>PMID:17223130</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 2im3" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_17223130}}, adds the Publication Abstract to the page
+*[[RNA polymerase 3D structures|RNA polymerase 3D structures]]
-(as it appears on PubMed at http://www.pubmed.gov), where 17223130 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_17223130}}
+__TOC__
+</StructureSection>
-==About this Structure==
+[[Category: Human poliovirus 1 Mahoney]]
-IM3 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Human_poliovirus_1 Human poliovirus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2IM3 OCA].
+[[Category: Large Structures]]
+[[Category: Peersen OB]]
-==Reference==
+[[Category: Thompson AA]]
-Stabilization of poliovirus polymerase by NTP binding and fingers-thumb interactions., Thompson AA, Albertini RA, Peersen OB, J Mol Biol. 2007 Mar 9;366(5):1459-74. Epub 2006 Dec 1. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17223130 17223130]
-[[Category: Human poliovirus 1]]
-[[Category: RNA-directed RNA polymerase]]
-[[Category: Single protein]]
-[[Category: Peersen, O B.]]
-[[Category: Thompson, A A.]]
-[[Category: 3d]]
-[[Category: Nucleotidyltransferase]]
-[[Category: Poliovirus]]
-[[Category: Polymerase]]
-[[Category: Rna-dependent]]
-[[Category: Stabilization]]
-[[Category: Utp]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 14:22:24 2008''