2a19
|
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.
DiseaseDisease
Known disease associated with this structure: Kallmann syndrome 3 OMIM:[607123]
About this StructureAbout this Structure
2A19 is a Protein complex structure of sequences from Homo sapiens and Saccharomyces cerevisiae with MG, PO4 and ANP as ligands. 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 Mon Nov 12 20:44:23 2007