6vvg

Publication Abstract from PubMed

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 alphaC 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 beta-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.

Granulovirus PK-1 kinase activity relies on a side-to-side dimerization mode centered on the regulatory alphaC 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 Nat Commun. 2021 Feb 12;12(1):1002. doi: 10.1038/s41467-021-21191-7. PMID:33579933^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.