PDBsum entry 2a19

Protein synthesis/transferase

PDB id: 2a19

Contents

Protein chains

165 a.a.

264 a.a.

203 a.a.

Ligands

ANP ×2

PO4

Metals

_MG ×4

Waters ×72

References listed in PDB file

Key reference

Title

Higher-Order substrate recognition of eif2alpha by the RNA-Dependent protein kinase pkr.

Authors

A.C.Dar, T.E.Dever, F.Sicheri.

Ref.

Cell, 2005, 122, 887-900. [DOI no: 10.1016/j.cell.2005.06.044]

PubMed id

16179258

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.

Figure 1.
Figure 1. Structure of the PKR-eIF2α Complex

Figure 2.
Figure 2. Active-Site Structure of PKR

The above figures are reprinted by permission from Cell Press: Cell (2005, 122, 887-900) copyright 2005.