View source for 2kaf


==Solution structure of the SARS-unique domain-C from the nonstructural protein 3 (nsp3) of the severe acute respiratory syndrome coronavirus==
<StructureSection load='2kaf' size='340' side='right' caption='[[2kaf]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2kaf]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Cvhsa Cvhsa]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KAF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2KAF FirstGlance]. <br>
</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">1a ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=227859 CVHSA])</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=2kaf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kaf OCA], [http://pdbe.org/2kaf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2kaf RCSB], [http://www.ebi.ac.uk/pdbsum/2kaf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2kaf ProSAT], [http://www.topsan.org/Proteins/JCSG/2kaf TOPSAN]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/R1A_CVHSA R1A_CVHSA]] The papain-like proteinase (PL-PRO) is responsible for the cleavages located at the N-terminus of replicase polyprotein. In addition, PL-PRO possesses a deubiquitinating/deISGylating activity and processes both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular substrates. Antagonizes innate immune induction of type I interferon by blocking the phosphorylation, dimerization and subsequent nuclear translocation of host IRF-3.<ref>PMID:17024178</ref> <ref>PMID:17692280</ref> <ref>PMID:19369340</ref>   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 (By similarity). Also contains an ADP-ribose-1''-phosphate (ADRP)-binding function.<ref>PMID:17024178</ref> <ref>PMID:17692280</ref> <ref>PMID:19369340</ref>   Nsp7-nsp8 hexadecamer may possibly confer processivity to the polymerase, maybe by binding to dsRNA or by producing primers utilized by the latter.<ref>PMID:17024178</ref> <ref>PMID:17692280</ref> <ref>PMID:19369340</ref>   Nsp9 is a ssRNA-binding protein.<ref>PMID:17024178</ref> <ref>PMID:17692280</ref> <ref>PMID:19369340</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Nonstructural protein 3 of the severe acute respiratory syndrome (SARS) coronavirus includes a "SARS-unique domain" (SUD) consisting of three globular domains separated by short linker peptide segments. This work reports NMR structure determinations of the C-terminal domain (SUD-C) and a two-domain construct (SUD-MC) containing the middle domain (SUD-M) and the C-terminal domain, and NMR data on the conformational states of the N-terminal domain (SUD-N) and the SUD-NM two-domain construct. Both SUD-N and SUD-NM are monomeric and globular in solution; in SUD-NM, there is high mobility in the two-residue interdomain linking sequence, with no preferred relative orientation of the two domains. SUD-C adopts a frataxin like fold and has structural similarity to DNA-binding domains of DNA-modifying enzymes. The structures of both SUD-M (previously determined) and SUD-C (from the present study) are maintained in SUD-MC, where the two domains are flexibly linked. Gel-shift experiments showed that both SUD-C and SUD-MC bind to single-stranded RNA and recognize purine bases more strongly than pyrimidine bases, whereby SUD-MC binds to a more restricted set of purine-containing RNA sequences than SUD-M. NMR chemical shift perturbation experiments with observations of (15)N-labeled proteins further resulted in delineation of RNA binding sites (i.e., in SUD-M, a positively charged surface area with a pronounced cavity, and in SUD-C, several residues of an anti-parallel beta-sheet). Overall, the present data provide evidence for molecular mechanisms involving the concerted actions of SUD-M and SUD-C, which result in specific RNA binding that might be unique to the SUD and, thus, to the SARS coronavirus.

SARS coronavirus unique domain: three-domain molecular architecture in solution and RNA binding.,Johnson MA, Chatterjee A, Neuman BW, Wuthrich K J Mol Biol. 2010 Jul 23;400(4):724-42. Epub 2010 May 21. PMID:20493876<ref>PMID:20493876</ref>

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

==See Also==
*[[Nonstructural protein|Nonstructural protein]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Cvhsa]]
[[Category: Buchmeier, M J]]
[[Category: Chatterjee, A]]
[[Category: Herrmann, T]]
[[Category: Structural genomic]]
[[Category: Johnson, M A]]
[[Category: Joseph, J]]
[[Category: Kuhn, P]]
[[Category: Mohanty, B]]
[[Category: Pedrini, B]]
[[Category: Saikatendu, K]]
[[Category: Serrano, P]]
[[Category: Wilson, I A]]
[[Category: Wuthrich, K]]
[[Category: Automation in nmr structure determination]]
[[Category: Nonstructural protein 3]]
[[Category: PSI, Protein structure initiative]]
[[Category: Rna binding protein]]
[[Category: Sars coronavirus]]
[[Category: Sars-unique domain-c]]
[[Category: Viral protein]]