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

Nat Commun. 2021 Feb 12;12(1):1002. doi: 10.1038/s41467-021-21191-7.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Baculoviridae / metabolism
  • Crystallography, X-Ray
  • Dimerization*
  • Granulovirus / enzymology*
  • Granulovirus / genetics
  • Molecular Dynamics Simulation
  • Phosphorylation
  • Protein Conformation
  • Protein Kinases / chemistry*
  • Protein Kinases / genetics
  • Protein Kinases / metabolism*
  • Protein Subunits / metabolism
  • Viral Proteins / metabolism

Substances

  • Protein Subunits
  • Viral Proteins
  • Protein Kinases