1qu6
From Proteopedia
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==Overview== | ==Overview== | ||
| - | Protein kinase PKR is an interferon-induced enzyme that plays a key role | + | 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. |
==Disease== | ==Disease== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Carpick, B | + | [[Category: Carpick, B W.]] |
[[Category: Nanduri, S.]] | [[Category: Nanduri, S.]] | ||
[[Category: Qin, J.]] | [[Category: Qin, J.]] | ||
| - | [[Category: Williams, B | + | [[Category: Williams, B R.G.]] |
[[Category: Yang, Y.]] | [[Category: Yang, Y.]] | ||
[[Category: dsrna-binding domain]] | [[Category: dsrna-binding domain]] | ||
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[[Category: solution structure]] | [[Category: solution structure]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:43:45 2008'' |
Revision as of 12:43, 21 February 2008
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STRUCTURE OF THE DOUBLE-STRANDED RNA-BINDING DOMAIN OF THE PROTEIN KINASE PKR REVEALS THE MOLECULAR BASIS OF ITS DSRNA-MEDIATED ACTIVATION
Contents |
Overview
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.
Disease
Known disease associated with this structure: Kallmann syndrome 3 OMIM:[607123]
About this Structure
1QU6 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structure of the double-stranded RNA-binding domain of the protein kinase PKR reveals the molecular basis of its dsRNA-mediated activation., Nanduri S, Carpick BW, Yang Y, Williams BR, Qin J, EMBO J. 1998 Sep 15;17(18):5458-65. PMID:9736623
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