View source for 3gzf


==Structure of the C-terminal domain of nsp4 from Feline Coronavirus==
<StructureSection load='3gzf' size='340' side='right' caption='[[3gzf]], [[Resolution|resolution]] 2.76&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3gzf]] is a 5 chain structure with sequence from [http://en.wikipedia.org/wiki/Fecv Fecv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3GZF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3GZF FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3gzf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gzf OCA], [http://pdbe.org/3gzf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3gzf RCSB], [http://www.ebi.ac.uk/pdbsum/3gzf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3gzf ProSAT]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/R1AB_FIPV R1AB_FIPV]] The replicase polyprotein of coronaviruses is a multifunctional protein: it contains the activities necessary for the transcription of negative stranded RNA, leader RNA, subgenomic mRNAs and progeny virion RNA as well as proteinases responsible for the cleavage of the polyprotein into functional products.  The papain-like proteinase 1 (PLP1) and papain-like proteinase 2 (PLP2) are responsible for the cleavages located at the N-terminus of the replicase polyprotein. In addition, PLP2 possesses a deubiquitinating/deISGylating activity and processes both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular substrates. PLP2 also antagonizes innate immune induction of type I interferon by blocking the nuclear translocation of host IRF-3 (By similarity).  The main proteinase 3CL-PRO is responsible for the majority of cleavages as it cleaves the C-terminus of replicase polyprotein at 11 sites. Recognizes substrates containing the core sequence [ILMVF]-Q-|-[SGACN]. Inhibited by the substrate-analog Cbz-Val-Asn-Ser-Thr-Leu-Gln-CMK. Also contains an ADP-ribose-1''-phosphate (ADRP)-binding function (By similarity).  The helicase which contains a zinc finger structure displays RNA and DNA duplex-unwinding activities with 5' to 3' polarity. ATPase activity is strongly stimulated by poly(U), poly(dT), poly(C), poly(dA), but not by poly(G) (By similarity).  The exoribonuclease acts on both ssRNA and dsRNA in a 3' to 5' direction (By similarity).  Nsp7-nsp8 hexadecamer may possibly confer processivity to the polymerase, maybe by binding to dsRNA or by producing primers utilized by the latter (By similarity).  Nsp9 is a ssRNA-binding protein (By similarity).  NendoU is a Mn(2+)-dependent, uridylate-specific enzyme, which leaves 2'-3'-cyclic phosphates 5' to the cleaved bond (By similarity). 
== 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/gz/3gzf_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=3gzf ConSurf].
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== Publication Abstract from PubMed ==
Coronaviruses are a family of positive-stranded RNA viruses that includes important pathogens of humans and other animals. The large coronavirus genome (26-31 kb) encodes 15-16 nonstructural proteins (nsps) that are derived from two replicase polyproteins by autoproteolytic processing. The nsps assemble into the viral replication-transcription complex and nsp3, nsp4 and nsp6 are believed to anchor this enzyme complex to modified intracellular membranes. The largest part of the coronavirus nsp4 subunit is hydrophobic and is predicted to be embedded in the membranes. In this report, a conserved C-terminal domain ( approximately 100 amino-acid residues) has been delineated that is predicted to face the cytoplasm and has been isolated as a soluble domain using library-based construct screening. A prototypical crystal structure at 2.8 A resolution was obtained using nsp4 from feline coronavirus. Unmodified and SeMet-substituted proteins were crystallized under similar conditions, resulting in tetragonal crystals that belonged to space group P4(3). The phase problem was initially solved by single isomorphous replacement with anomalous scattering (SIRAS), followed by molecular replacement using a SIRAS-derived composite model. The structure consists of a single domain with a predominantly alpha-helical content displaying a unique fold that could be engaged in protein-protein interactions.

Structure of the C-terminal domain of nsp4 from feline coronavirus.,Manolaridis I, Wojdyla JA, Panjikar S, Snijder EJ, Gorbalenya AE, Berglind H, Nordlund P, Coutard B, Tucker PA Acta Crystallogr D Biol Crystallogr. 2009 Aug;65(Pt 8):839-46. Epub 2009, Jul 17. PMID:19622868<ref>PMID:19622868</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 3gzf" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Fecv]]
[[Category: Coutard, B]]
[[Category: Gorbalenya, A E]]
[[Category: Manolaridis, I]]
[[Category: Panjikar, S]]
[[Category: Snijder, E J]]
[[Category: Tucker, P A]]
[[Category: Wojdyla, J A]]
[[Category: Coronavirus]]
[[Category: Fcov]]
[[Category: Nsp4]]
[[Category: Viral protein]]