2A19

PKR kinase domain- eIF2alpha- AMP-PNP complex.

Summary for 2A19

• Entry DOI: 10.2210/pdb2a19/pdb
• Related: 2a1a
• Descriptor: Eukaryotic translation initiation factor 2 alpha subunit, Interferon-induced, double-stranded RNA-activated protein kinase, MAGNESIUM ION, ... (6 entities in total)
• Functional Keywords: transferase, kinase, protein biosynthesis, protein synthesis-transferase complex, protein synthesis/transferase
• Biological source: Saccharomyces cerevisiae (baker's yeast); More
• Total number of polymer chains: 3
• Total formula weight: 87357.47

Authors

Dar, A.C.,Dever, T.E.,Sicheri, F. (deposition date: 2005-06-19, release date: 2005-09-27, Last modification date: 2024-10-09)

Primary citation

Dar, A.C.,Dever, T.E.,Sicheri, F.
Higher-Order Substrate Recognition of eIF2alpha by the RNA-Dependent Protein Kinase PKR.
Cell(Cambridge,Mass.), 122:887-900, 2005

PubMed Abstract: 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.

PubMed: 16179258
DOI: 10.1016/j.cell.2005.06.044

Experimental method

X-RAY DIFFRACTION (2.5 Å)