Granulovirus PK-1 kinase activity relies on a side-to-side dimerization mode centered on the regulatory αC helix

Michael R. Oliver, Christopher R. Horne, Safal Shrestha, Jeremy R. Keown, Lung-Yu Liang, Samuel N. Young, Jarrod J. Sandow, Andrew I. Webb, David C. Goldstone, Isabelle S. Lucet, Natarajan Kannan, Peter Metcalf, James M. Murphy

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Article number1002
Number of pages11
JournalNature Communications
Volume12
Issue number1
DOIs
Publication statusPublished - 12 Feb 2021

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