Download MendeleyGranulovirus PK-1 kinase activity relies on a side-to-side dimerization mode centered on the regulatory alpha C helix.
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., Murphy, J.M.(2021) Nat Commun 12: 1002-1002
- PubMed: 33579933
- DOI: https://doi.org/10.1038/s41467-021-21191-7
- Primary Citation of Related Structures:
6VVG - PubMed 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.
Organizational Affiliation:
School of Biological Sciences, University of Auckland, Auckland, New Zealand.
