6D3K
Crystal structure of unphosphorylated human PKR kinase domain in complex with ADP
Summary for 6D3K
| Entry DOI | 10.2210/pdb6d3k/pdb |
| Descriptor | Interferon-induced, double-stranded RNA-activated protein kinase, ADENOSINE-5'-DIPHOSPHATE, PHOSPHATE ION, ... (6 entities in total) |
| Functional Keywords | unphosphorylated, kinase, complex, activation loop swapping, dimer, transferase |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 3 |
| Total formula weight | 114744.16 |
| Authors | Erlandsen, H.,Mayo, C.B.,Robinson, V.L.,Cole, J.L. (deposition date: 2018-04-16, release date: 2019-07-10, Last modification date: 2023-10-04) |
| Primary citation | Mayo, C.B.,Erlandsen, H.,Mouser, D.J.,Feinstein, A.G.,Robinson, V.L.,May, E.R.,Cole, J.L. Structural Basis of Protein Kinase R Autophosphorylation. Biochemistry, 58:2967-2977, 2019 Cited by PubMed Abstract: 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 eIF2α. PubMed: 31246429DOI: 10.1021/acs.biochem.9b00161 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.6 Å) |
Structure validation
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