A.Flayhan
et al.
(2015).
The structure of Legionella pneumophila LegK4 type four secretion system (T4SS) effector reveals a novel dimeric eukaryotic-like kinase.
Sci Rep,
5,
14602.
PubMed id: 26419332
DOI: 10.1038/srep14602
Bacterial pathogens subvert signalling pathways to promote invasion and/or
replication into the host. LegK1-4 proteins are eukaryotic-like serine/threonine
kinases that are translocated by the Dot/Icm type IV secretion system (T4SS) of
several Legionella pneumophila strains. We present the crystal structures of an
active fragment of the LegK4 protein in apo and substrate-bound states. The
structure of LegK4(1-445) reveals a eukaryotic-like kinase domain flanked by a
novel cap domain and a four-helix bundle. The protein self-assembles through
interactions mediated by helices αF and αG that generate a dimeric interface
not previously observed in a protein kinase. The helix αG is displaced compared
to previous kinase structures, and its role in stabilization of the activation
loop is taken on by the dimerisation interface. The apo-form of the protein has
an open conformation with a disordered P-loop but a structured activation
segment in absence of targeted phosphorylation. The nucleotide-binding site of
LegK4 contains an unusual set of residues that mediate non-canonical
interactions with AMP-PNP. Nucleotide binding results in limited changes in the
active site, suggesting that LegK4 constitutive kinase activity does not depend
on phosphorylation of the activation loop but on the stabilizing effects of the
dimer.
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