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A dynamically tuned double‐stranded RNA binding mechanism for the activation of antiviral kinase PKR
Author(s) -
Nanduri Sambasivarao,
Rahman Fahima,
Williams Bryan R. G.,
Qin Jun
Publication year - 2000
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/19.20.5567
Subject(s) - biology , protein kinase r , eif 2 kinase , mechanism (biology) , rna , kinase , microbiology and biotechnology , virology , protein kinase a , mitogen activated protein kinase kinase , genetics , cyclin dependent kinase 2 , gene , philosophy , epistemology
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.