2a19: Difference between revisions

Revision as of 18:28, 3 May 2008

PKR kinase domain- eIF2alpha- AMP-PNP complex.

OverviewOverview

In response to binding viral double-stranded RNA byproducts within a cell, the RNA-dependent protein kinase PKR phosphorylates the alpha subunit of the translation initiation factor eIF2 on a regulatory site, Ser51. This triggers the general shutdown of protein synthesis and inhibition of viral propagation. To understand the basis for substrate recognition by and the regulation of PKR, we determined X-ray crystal structures of the catalytic domain of PKR in complex with eIF2alpha. The structures reveal that eIF2alpha binds to the C-terminal catalytic lobe while catalytic-domain dimerization is mediated by the N-terminal lobe. In addition to inducing a local unfolding of the Ser51 acceptor site in eIF2alpha, its mode of binding to PKR affords the Ser51 site full access to the catalytic cleft of PKR. The generality and implications of the structural mechanisms uncovered for PKR to the larger family of four human eIF2alpha protein kinases are discussed.

About this StructureAbout this Structure

2A19 is a Protein complex structure of sequences from Homo sapiens and Saccharomyces cerevisiae. Full crystallographic information is available from OCA.

ReferenceReference

Higher-order substrate recognition of eIF2alpha by the RNA-dependent protein kinase PKR., Dar AC, Dever TE, Sicheri F, Cell. 2005 Sep 23;122(6):887-900. PMID:16179258 Page seeded by OCA on Sat May 3 18:28:41 2008

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OCA

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 [[Image:2a19.gif|left|200px]]
- {{Structure
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-|GENE= SUI2, TIF211 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 Saccharomyces cerevisiae]), PRKR, EIF2AK2, PKR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
+-->
-|DOMAIN=
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-|RELATEDENTRY=[[2a1a|2a1a]]
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2a19 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2a19 OCA], [http://www.ebi.ac.uk/pdbsum/2a19 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2a19 RCSB]</span>
-}}
 '''PKR kinase domain- eIF2alpha- AMP-PNP complex.'''
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 [[Category: Dever, T E.]]
 [[Category: Sicheri, F.]]
-[[Category: kinase]]
+[[Category: Kinase]]
-[[Category: protein biosynthesis]]
+[[Category: Protein biosynthesis]]
-[[Category: transferase]]
+[[Category: Transferase]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 18:28:41 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:46:28 2008''