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6d3k

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Revision as of 08:32, 24 July 2019

Crystal structure of unphosphorylated human PKR kinase domain in complex with ADP

Structural highlights

6d3k is a 3 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , ,
Gene:	EIF2AK2, PKR, PRKR (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[E2AK2_HUMAN] Following activation by double-stranded RNA in the presence of ATP, the kinase becomes autophosphorylated and can catalyze the phosphorylation of the translation initiation factor EIF2S1, which leads to an inhibition of the initiation of protein synthesis. Double-stranded RNA is generated during the course of a viral infection. In addition to serine/threonine-protein kinase activity, also has tyrosine-protein kinase activity: phosphorylates CDK1 upon DNA damage. CDK1 phosphorylation triggers CDK1 polyubiquitination and subsequent proteolysis, thus leading to G2 arrest.^[1]

Publication Abstract from PubMed

The RNA-activated protein kinase, PKR, is a key mediator of the innate immunity response to viral infection. Viral double-stranded RNAs induce PKR dimerization and autophosphorylation. The PKR kinase domain forms a back-to-back dimer. However, intermolecular ( trans) autophosphorylation is not feasible in this arrangement. We have obtained PKR kinase structures that resolves this dilemma. The kinase protomers interact via the known back-to-back interface as well as a front-to-front interface that is formed by exchange of activation segments. Mutational analysis of the front-to-front interface support a functional role in PKR activation. Molecular dynamics simulations reveal that the activation segment is highly dynamic in the front-to-front dimer and can adopt conformations conducive to phosphoryl transfer. We propose a mechanism where back-to-back dimerization induces a conformational change that activates PKR to phosphorylate a "substrate" kinase docked in a front-to-front geometry. This mechanism may be relevant to related kinases that phosphorylate the eukaryotic initiation factor eIF2alpha.

Structural Basis of Protein Kinase R Autophosphorylation.,Mayo CB, Erlandsen H, Mouser DJ, Feinstein AG, Robinson VL, May ER, Cole JL Biochemistry. 2019 Jul 9;58(27):2967-2977. doi: 10.1021/acs.biochem.9b00161. Epub, 2019 Jun 27. PMID:31246429^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Yoon CH, Miah MA, Kim KP, Bae YS. New Cdc2 Tyr 4 phosphorylation by dsRNA-activated protein kinase triggers Cdc2 polyubiquitination and G2 arrest under genotoxic stresses. EMBO Rep. 2010 May;11(5):393-9. doi: 10.1038/embor.2010.45. Epub 2010 Apr 16. PMID:20395957 doi:http://dx.doi.org/10.1038/embor.2010.45
↑ Mayo CB, Erlandsen H, Mouser DJ, Feinstein AG, Robinson VL, May ER, Cole JL. Structural Basis of Protein Kinase R Autophosphorylation. Biochemistry. 2019 Jul 9;58(27):2967-2977. doi: 10.1021/acs.biochem.9b00161. Epub, 2019 Jun 27. PMID:31246429 doi:http://dx.doi.org/10.1021/acs.biochem.9b00161

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6d3k"

@@ Line 3: / Line 3: @@
 <StructureSection load='6d3k' size='340' side='right'caption='[[6d3k]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6d3k]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6D3K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6D3K FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6d3k]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6D3K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6D3K FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">EIF2AK2, PKR, PRKR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6d3k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d3k OCA], [http://pdbe.org/6d3k PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6d3k RCSB], [http://www.ebi.ac.uk/pdbsum/6d3k PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6d3k ProSAT]</span></td></tr>
 </table>
@@ Line 22: / Line 23: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Large Structures]]
 [[Category: Cole, J L]]

6d3k

From Proteopedia

Revision as of 08:32, 24 July 2019

Crystal structure of unphosphorylated human PKR kinase domain in complex with ADP

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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