1QU6

STRUCTURE OF THE DOUBLE-STRANDED RNA-BINDING DOMAIN OF THE PROTEIN KINASE PKR REVEALS THE MOLECULAR BASIS OF ITS DSRNA-MEDIATED ACTIVATION

Summary for 1QU6

• Entry DOI: 10.2210/pdb1qu6/pdb
• Descriptor: PROTEIN KINASE PKR (1 entity in total)
• Functional Keywords: dsrna-binding domain, pkr, solution structure, protein kinase, transferase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 19705.42

Authors

Nanduri, S.,Carpick, B.W.,Yang, Y.,Williams, B.R.G.,Qin, J. (deposition date: 1999-07-08, release date: 1999-12-23, Last modification date: 2023-12-27)

Primary citation

Nanduri, S.,Carpick, B.W.,Yang, Y.,Williams, B.R.,Qin, J.
Structure of the double-stranded RNA-binding domain of the protein kinase PKR reveals the molecular basis of its dsRNA-mediated activation.
EMBO J., 17:5458-5465, 1998

PubMed Abstract: Protein kinase PKR is an interferon-induced enzyme that plays a key role in the control of viral infections and cellular homeostasis. Compared with other known kinases, PKR is activated by a distinct mechanism that involves double-stranded RNA (dsRNA) binding in its N-terminal region in an RNA sequence-independent fashion. We report here the solution structure of the 20 kDa dsRNA-binding domain (dsRBD) of human PKR, which provides the first three-dimensional insight into the mechanism of its dsRNA-mediated activation. The structure of dsRBD exhibits a dumb-bell shape comprising two tandem linked dsRNA-binding motifs (dsRBMs) both with an alpha-beta-beta-beta-alpha fold. The structure, combined with previous mutational and biochemical data, reveals a highly conserved RNA-binding site on each dsRBM and suggests a novel mode of protein-RNA recognition. The central linker is highly flexible, which may enable the two dsRBMs to wrap around the RNA duplex for cooperative and high-affinity binding, leading to the overall change of PKR conformation and its activation.

PubMed: 9736623
DOI: 10.1093/emboj/17.18.5458

Experimental method

SOLUTION NMR