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A dynamically tuned double‐stranded RNA binding mechanism for the activation of antiviral kinase PKR

A dynamically tuned double‐stranded RNA binding mechanism for the activation of antiviral kinase PKR A key step in the activation of interferon‐inducible antiviral kinase PKR involves differential binding of viral double‐stranded RNA (dsRNA) to its two structurally similar N‐terminal dsRNA binding motifs, dsRBM1 and dsRBM2. We show here, using NMR spectroscopy, that dsRBM1 with higher RNA binding activity exhibits significant motional flexibility on a millisecond timescale as compared with dsRBM2 with lower RNA binding activity. We further show that dsRBM2, but not dsRBM1, specifically interacts with the C‐terminal kinase domain. These results suggest a dynamically tuned dsRNA binding mechanism for PKR activation, where motionally more flexible dsRBM1 anchors to dsRNA, thereby inducing a cooperative RNA binding for dsRBM2 to expose the kinase domain. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The EMBO Journal Wiley

A dynamically tuned double‐stranded RNA binding mechanism for the activation of antiviral kinase PKR

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References (34)

Publisher
Wiley
Copyright
Copyright © 2013 Wiley Periodicals, Inc
ISSN
0261-4189
eISSN
1460-2075
DOI
10.1093/emboj/19.20.5567
pmid
11032824
Publisher site
See Article on Publisher Site

Abstract

A key step in the activation of interferon‐inducible antiviral kinase PKR involves differential binding of viral double‐stranded RNA (dsRNA) to its two structurally similar N‐terminal dsRNA binding motifs, dsRBM1 and dsRBM2. We show here, using NMR spectroscopy, that dsRBM1 with higher RNA binding activity exhibits significant motional flexibility on a millisecond timescale as compared with dsRBM2 with lower RNA binding activity. We further show that dsRBM2, but not dsRBM1, specifically interacts with the C‐terminal kinase domain. These results suggest a dynamically tuned dsRNA binding mechanism for PKR activation, where motionally more flexible dsRBM1 anchors to dsRNA, thereby inducing a cooperative RNA binding for dsRBM2 to expose the kinase domain.

Journal

The EMBO JournalWiley

Published: Apr 16, 2001

Keywords: ; ; ;

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