Specific recognition of HIV TAR RNA by the dsRNA binding domains (dsRBD1-dsRBD2) of PKR

Journal of Molecular Biology
Insil KimJoseph D Puglisi

Abstract

PKR (double-stranded RNA-dependent protein kinase) is an important component of host defense to virus infection. Binding of dsRNA to two dsRBDs (double-stranded RNA binding domains) of PKR modulates its own kinase activation. How structural features of natural target RNAs, such as bulges and loops, have an effect on the binding to two dsRBDs of PKR still remains unclear. By using ITC and NMR, we show here that both the bulge and loop of TAR RNA are necessary for the high affinity binding to dsRBD1-dsRBD2 of PKR with 1:1 stoichiometry. The binding site for the dsRBD1-dsRBD2 spans from upper bulge to lower stem of the TAR RNA, based on chemical shift mapping. The backbone resonances in the 40 kDa TAR.dsRBD1-dsRBD2 were assigned. NMR chemical shift perturbation data suggest that the beta1-beta2 loop of the dsRBD1 interacts with the TAR RNA, whereas that of the dsRBD2 is less involved in the TAR RNA recognition. In addition, the residues of the interdomain linker between the dsRBD1 and the dsRBD2 also show large chemical perturbations indicating that the linker is involved in the recognition of TAR RNA. The results presented here provide the biophysical and spectroscopic basis for high-resolution structural studies, and show how lo...Continue Reading

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Citations

Dec 15, 2007·Nature Protocols·Sean A McKennaJoseph D Puglisi
May 3, 2007·Nature Reviews. Molecular Cell Biology·Bradley M LundeGabriele Varani
Sep 1, 2009·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Cyril X GeorgeCharles E Samuel
Dec 13, 2006·Microbiology and Molecular Biology Reviews : MMBR·M A GarcíaM Esteban
Sep 11, 2012·Cellular and Molecular Life Sciences : CMLS·Alys Peisley, Sun Hur
Jul 1, 2014·Proceedings of the National Academy of Sciences of the United States of America·Janghyun LeeHashim M Al-Hashimi
Dec 14, 2011·Journal of Molecular Biology·Jeffrey D LevengoodBlanton S Tolbert
Jul 10, 2007·Journal of Molecular Biology·Sean A McKennaJoseph D Puglisi
Apr 25, 2007·Biochimie·M A GarcíaM Esteban
Feb 5, 2011·Reviews in Medical Virology·Guerline ClerziusAnne Gatignol
Apr 4, 2006·Journal of Molecular Biology·Sean A McKennaJoseph D Puglisi
May 19, 2009·Journal of Molecular Biology·Laurie A HeinickePhilip C Bevilacqua
Jul 5, 2008·Journal of Molecular Biology·Peter A LemaireJames L Cole
Nov 8, 2013·Scientific Reports·Hong Yan Liu, Xiaohu Gao
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Feb 8, 2007·The Journal of Biological Chemistry·Sean A McKennaJoseph D Puglisi
Mar 19, 2009·Journal of the American Chemical Society·Hillary Workman, Peter F Flynn
Oct 3, 2006·Journal of Molecular Biology·Vladimir GelevGerhard Wagner

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