Granulovirus PK-1 kinase activity relies on a side-to-side dimerization mode centered on the regulatory αC helix
- Oliver, MR; Horne, CR; Shrestha, S; Keown, JR; Liang, LY; Young, SN; Sandow, JJ; Webb, AI; Goldstone, DC; Lucet, IS; Kannan, N; Metcalf, P; Murphy, JM;
Publication Year 2021-02-12, Volume 12, Issue #1, Page 1002
- Journal Title
- Nature Communications
- 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.
- WEHI Research Division(s)
- Inflammation; Chemical Biology; Advanced Technology And Biology
- PubMed ID
- Publisher's Version
- Open Access at Publisher's Site
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- Refer to copyright notice on published article.
Creation Date: 2021-03-09 01:36:58Last Modified: 2021-03-09 02:43:11