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PDBsum entry 2onl
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References listed in PDB file
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Key reference
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Title
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Crystal structure of the p38 alpha-Mapkap kinase 2 heterodimer.
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Authors
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E.Ter haar,
P.Prabakhar,
X.Liu,
C.Lepre.
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Ref.
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J Biol Chem, 2007,
282,
9733-9739.
[DOI no: ]
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PubMed id
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Abstract
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The p38 signaling pathway is activated in response to cell stress and induces
production of proinflammatory cytokines. P38alpha is phosphorylated and
activated in response to cell stress by MKK3 and MKK6 and in turn phosphorylates
a number of substrates, including MAPKAP kinase 2 (MK2). We have determined the
crystal structure of the unphosphorylated p38alpha-MK2 heterodimer. The
C-terminal regulatory domain of MK2 binds in the docking groove of p38alpha, and
the ATP-binding sites of both kinases are at the heterodimer interface. The
conformation suggests an extra mechanism in addition to the regulation of the
p38alpha and MK2 phosphorylation states that prevents phosphorylation of
substrates in the absence of cell stress. Addition of constitutively active
MKK6-DD results in rapid phosphorylation of the p38alpha-MK2 heterodimer.
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Figure 1.
FIGURE 1. Crystal structure of the p38  -MK2 heterodimer. A,
side view of the p38 -MK2 heterodimer. P38
(yellow) and MK2
(magenta) are positioned "face to face" in the heterodimer,
which means that the ATP-binding sites and the substrate binding
grooves are at the interface of the heterodimer. The K-helix
of the MK2 C-terminal regulatory domain (blue) is sandwiched
between the p38 and MK2 kinase domains,
whereas residues 370–393 of the C-terminal regulatory domain
bind p38 in the docking groove.
B, heterodimer rotated 180°. C, top view of the heterodimer.
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Figure 3.
FIGURE 3. Binding of MK2 C-terminal regulatory domain in
the p38 docking groove. The MK2
C-terminal regulatory domain binds both the common docking site
(A) and the ED site (B). The side chains of Ala^378, Ser^379,
Leu^384, and Lys^388 of MK2 have been omitted for clarity. The
side chains of p38 are colored yellow. MK2
is colored purple.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2007,
282,
9733-9739)
copyright 2007.
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