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

Oliver, M. R. et al. (2021) Granulovirus PK-1 kinase activity relies on a side-to-side dimerization mode centered on the regulatory αC helix. Nature Communications, 12, 1002. (doi: 10.1038/s41467-021-21191-7) (PMID:33579933) (PMCID:PMC7881018)

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.

• Item Type: Articles
• Additional Information: J.M.M. gratefully acknowledges National Health and Medical Research Council of Australia support (Investigator grant 1172929 and IRIISS grant 9000653) and the Victorian Government Operational Infrastructure Support Scheme. Funding for N.K. from the National Institutes of Health (R01GM114409) is acknowledged. P.M. gratefully acknowledges support of the New Zealand Royal Society Marsden (grant UOA221).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Oliver, Dr Michael
• Authors: Oliver, M. R., Horne, C. R., Shrestha, S., Keown, J. R., Liang, L.-Y., Young, S. N., Sandow, J. J., Webb, A. I., Goldstone, D. C., Lucet, I. S., Kannan, N., Metcalf, P., and Murphy, J. M.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Nature Communications
• Publisher: Nature Research
• ISSN: 2041-1723
• ISSN (Online): 2041-1723
• Copyright Holders: Copyright © 2021 The Author(s)
• First Published: First published in Nature Communications 12:1002
• Publisher Policy: Reproduced under a Creative Commons license