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PDBsum entry 4lqq
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Transferase/transferase activator
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PDB id
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4lqq
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Contents |
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388 a.a.
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146 a.a.
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329 a.a.
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137 a.a.
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References listed in PDB file
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Key reference
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Title
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The structure of an ndr/lats kinase-Mob complex reveals a novel kinase-Coactivator system and substrate docking mechanism.
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Authors
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G.Gógl,
K.D.Schneider,
B.J.Yeh,
N.Alam,
A.N.Nguyen ba,
A.M.Moses,
C.Hetényi,
A.Reményi,
E.L.Weiss.
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Ref.
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Plos Biol, 2015,
13,
e1002146.
[DOI no: ]
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PubMed id
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Abstract
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Eukaryotic cells commonly use protein kinases in signaling systems that relay
information and control a wide range of processes. These enzymes have a
fundamentally similar structure, but achieve functional diversity through
variable regions that determine how the catalytic core is activated and
recruited to phosphorylation targets. "Hippo" pathways are ancient
protein kinase signaling systems that control cell proliferation and
morphogenesis; the NDR/LATS family protein kinases, which associate with
"Mob" coactivator proteins, are central but incompletely understood
components of these pathways. Here we describe the crystal structure of budding
yeast Cbk1-Mob2, to our knowledge the first of an NDR/LATS kinase-Mob complex.
It shows a novel coactivator-organized activation region that may be unique to
NDR/LATS kinases, in which a key regulatory motif apparently shifts from an
inactive binding mode to an active one upon phosphorylation. We also provide a
structural basis for a substrate docking mechanism previously unknown in AGC
family kinases, and show that docking interaction provides robustness to Cbk1's
regulation of its two known in vivo substrates. Co-evolution of docking motifs
and phosphorylation consensus sites strongly indicates that a protein is an in
vivo regulatory target of this hippo pathway, and predicts a new group of
high-confidence Cbk1 substrates that function at sites of cytokinesis and cell
growth. Moreover, docking peptides arise in unstructured regions of proteins
that are probably already kinase substrates, suggesting a broad sequential model
for adaptive acquisition of kinase docking in rapidly evolving intrinsically
disordered polypeptides.
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