Granulovirus PK-1 kinase activity relies on a side-to-side dimerization mode centered on the regulatory αC helix
Michael R. Oliver,Michael R. Oliver,Christopher R Horne,Christopher R Horne,Safal Shrestha,J.R. Keown,J.R. Keown,Lung-Yu Liang,Lung-Yu Liang,Samuel N. Young,Jarrod J. Sandow,Jarrod J. Sandow,Andrew I. Webb,Andrew I. Webb,David C. Goldstone,Isabelle S Lucet,Isabelle S Lucet,Natarajan Kannan,Peter Metcalf,James M. Murphy,James M. Murphy +20 more
TLDR
In this article, the crystal structure of Cydia pomenella granulovirus PK-1 has been reported, where an antiparallel arrangement of the αC helices at the dimer core stabilizes the protein in a closed, active conformation.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.read more
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There's more to death than life: Noncatalytic functions in kinase and pseudokinase signaling.
TL;DR: A review of the non-catalytic functions of protein kinases can be found in this paper, where the authors consider pseudokinases, proteins that are devoid of enzymatic activity altogether and demonstrate that, beyond conventional notions of kinase function, catalytic activity can be dispensable for biological function.
Journal ArticleDOI
The intracellular domains of the EphB6 and EphA10 receptor tyrosine pseudokinases function as dynamic signalling hubs.
Lung-Yu Liang,Lung-Yu Liang,M.J. Roy,M.J. Roy,Christopher R Horne,Christopher R Horne,Jarrod J. Sandow,Jarrod J. Sandow,Minglyanna Surudoi,Laura F. Dagley,Laura F. Dagley,Samuel N. Young,Toby A. Dite,Toby A. Dite,Jeffrey J. Babon,Jeffrey J. Babon,Peter W. Janes,Onisha Patel,Onisha Patel,James M. Murphy,James M. Murphy,Isabelle S Lucet,Isabelle S Lucet +22 more
TL;DR: In this article, the authors characterized the biochemical properties and topology of EphB6 and EphA10 intracellular regions comprising the juxtamembrane (JM) region, pseudokinase and SAM domains.
Book ChapterDOI
Co-expression of recombinant RIPK3:MLKL complexes using the baculovirus-insect cell system.
TL;DR: In this paper , the authors describe methods for co-expression of pseudokinases and their interactors in insect cells, as exemplified by the MLKL pseudokinase, which is the terminal effector in the necroptosis cell death pathway, and its upstream regulator kinase RIPK3.
Posted ContentDOI
Nanobodies identify an activated state of the TRIB2 pseudokinase
Sam A. Jamieson,Michael Pudjihartono,Christopher R Horne,Robert C. Day,James M. Murphy,Peter D. Mace +5 more
TL;DR: In combination, this study identifies features of TRIB2 that could be exploited for the development of inhibitors, and nanobody tools for future investigation ofTRIB1–3 function.
Journal ArticleDOI
Nanobodies identify an activated state of the TRIB2 pseudokinase
TL;DR: In this paper , the TRIB2-Nb4.103 complex was identified as a nanobody that can stabilize TRIB 2 pseudokinase domain dimer in a face-to-face manner.
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