Journal article
Granulovirus PK-1 kinase activity relies on a side-to-side dimerization mode centered on the regulatory alpha C helix
Michael R Oliver, Christopher R Horne, Safal Shrestha, Jeremy R Keown, Lung-Yu Liang, Samuel N Young, Jarrod J Sandow, Andrew Webb, David C Goldstone, Isabelle S Lucet, Natarajan Kannan, Peter Metcalf, James M Murphy
NATURE COMMUNICATIONS | NATURE RESEARCH | Published : 2021
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-s..
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Awarded by National Health and Medical Research Council of Australia
Awarded by National Health and Medical Research Council of Australia (IRIISS)
Awarded by National Institutes of Health
Awarded by New Zealand Royal Society Marsden
Funding Acknowledgements
We thank staff at the Australian Synchrotron MX2 and SAXS/WAXS beamlines for their assistance in data collection and the New Zealand Synchrotron Group for enabling access; Yee-Foong Mok (Bio21 Institute, University of Melbourne) for assistance with analytical ultracentrifugation experiments. 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).