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.
Highlights
The life cycle of Baculoviridae family insect viruses depends on the viral protein kinase, protein kinase-1 (PK-1), to phosphorylate the regulatory protein, p6.9, to induce baculoviral genome release
Phosphorylation of p6.9 is mediated by protein kinase-1 (PK-1), a protein kinase expressed within the nucleocapsid of lepidopteran-infecting baculoviruses[14,15,16,17]
Our sequence analyses indicate a eukaryotic ancestral origin of PK-1, where the kinase was acquired via co-opting features from multiple eukaryotic kinases, in particular ribosomal protein S6 kinase A5 (RPS6KA5) from the insect host over its evolutionary trajectory
Summary
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. The unusual parallel, side-to-side arrangement of kinase domains within the dimer, characterized by the N-lobe:N-lobe and C-lobe:C-lobe interactions revealed by our crystal structure, positions each active site facing in opposing directions and primed for substrate engagement.
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