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PDBsum entry 3bq7
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References listed in PDB file
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Key reference
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Title
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Regulation of enzyme localization by polymerization: polymer formation by the sam domain of diacylglycerol kinase delta1.
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Authors
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B.T.Harada,
M.J.Knight,
S.Imai,
F.Qiao,
R.Ramachander,
M.R.Sawaya,
M.Gingery,
F.Sakane,
J.U.Bowie.
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Ref.
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Structure, 2008,
16,
380-387.
[DOI no: ]
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PubMed id
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Abstract
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The diacylglycerol kinase (DGK) enzymes function as regulators of intracellular
signaling by altering the levels of the second messengers, diacylglycerol and
phosphatidic acid. The DGK delta and eta isozymes possess a common
protein-protein interaction module known as a sterile alpha-motif (SAM) domain.
In DGK delta, SAM domain self-association inhibits the translocation of DGK
delta to the plasma membrane. Here we show that DGK delta SAM forms a polymer
and map the polymeric interface by a genetic selection for soluble mutants. A
crystal structure reveals that DGKSAM forms helical polymers through a
head-to-tail interaction similar to other SAM domain polymers. Disrupting
polymerization by polymer interface mutations constitutively localizes DGK delta
to the plasma membrane. Thus, polymerization of DGK delta regulates the activity
of the enzyme by sequestering DGK delta in an inactive cellular location.
Regulation by dynamic polymerization is an emerging theme in signal transduction.
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Figure 1.
Figure 1. Electron Micrograph of DGKSAM
Electron
microscopy image of DGKSAM revealing the formation of fibers.
Although most fibers are tangled, measurements of single fibers
show an average width of  vert,
similar 80 Å. Scale bar = 25 nm.
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Figure 3.
Figure 3. Crystal Structure of the DGKSAM Polymer
(A)
Space-filling model of the DGKSAM polymer showing the helical
structure. Every other subunit is colored green or yellow. Two
of the subunits are shown as ribbon diagrams.
(B) A ribbon
model showing a close-up view of the oligomeric interface. The
end-helix (EH, green) surface of one SAM domain contacts the
mid-loop (ML, yellow) surface of another SAM domain forming
head-to-tail interaction. Side-chains important in mediating
this interaction are shown and colored according to the surface
on which they reside. For sequence orientation: The V52, G53,
K56, E35G, and D43 in the DGKSAM structure correspond to V1148,
G1149, K1152, E1131, D1139, and C1116 in the full-length DGKδ1.
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The above figures are
reprinted
by permission from Cell Press:
Structure
(2008,
16,
380-387)
copyright 2008.
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