1. Granulovirus PK-1 kinase activity relies on a side-to-side dimerization mode centered on the regulatory αC helix.
- Author
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Oliver MR, Horne CR, Shrestha S, Keown JR, Liang LY, Young SN, Sandow JJ, Webb AI, Goldstone DC, Lucet IS, Kannan N, Metcalf P, and Murphy JM
- Subjects
- Baculoviridae metabolism, Crystallography, X-Ray, Granulovirus genetics, Molecular Dynamics Simulation, Phosphorylation, Protein Conformation, Protein Kinases genetics, Protein Subunits metabolism, Viral Proteins metabolism, Dimerization, Granulovirus enzymology, Protein Kinases chemistry, Protein Kinases metabolism
- Abstract
The life cycle of Baculoviridae family insect viruses depends on the viral protein kinase, PK-1, to phosphorylate the regulatory protein, p6.9, to induce baculoviral genome release. Here, we report the crystal structure of Cydia pomenella granulovirus PK-1, which, owing to its likely ancestral origin among host cell AGC kinases, exhibits a eukaryotic protein kinase fold. PK-1 occurs as a rigid dimer, where an antiparallel arrangement of the αC helices at the dimer core stabilizes PK-1 in a closed, active conformation. Dimerization is facilitated by C-lobe:C-lobe and N-lobe:N-lobe interactions between protomers, including the domain-swapping of an N-terminal helix that crowns a contiguous β-sheet formed by the two N-lobes. PK-1 retains a dimeric conformation in solution, which is crucial for catalytic activity. Our studies raise the prospect that parallel, side-to-side dimeric arrangements that lock kinase domains in a catalytically-active conformation could function more broadly as a regulatory mechanism among eukaryotic protein kinases.
- Published
- 2021
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