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PDBsum entry 2e4u
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Signaling protein
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PDB id
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2e4u
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References listed in PDB file
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Key reference
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Title
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Structures of the extracellular regions of the group ii/III metabotropic glutamate receptors.
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Authors
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T.Muto,
D.Tsuchiya,
K.Morikawa,
H.Jingami.
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Ref.
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Proc Natl Acad Sci U S A, 2007,
104,
3759-3764.
[DOI no: ]
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PubMed id
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Abstract
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Metabotropic glutamate receptors play major roles in the activation of
excitatory synapses in the central nerve system. We determined the crystal
structure of the entire extracellular region of the group II receptor and that
of the ligand-binding region of the group III receptor. A comparison among
groups I, II, and III provides the structural basis that could account for the
discrimination of group-specific agonists. Furthermore, the structure of group
II includes the cysteine-rich domain, which is tightly linked to the
ligand-binding domain by a disulfide bridge, suggesting a potential role in
transmitting a ligand-induced conformational change into the downstream
transmembrane region. The structure also reveals the lateral interaction between
the two cysteine-rich domains, which could stimulate clustering of the dimeric
receptors on the cell surface. We propose a general activation mechanism of the
dimeric receptor coupled with both ligand-binding and interprotomer
rearrangements.
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Figure 3.
Fig. 3. Agonist recognition by mGluR-II[3]. Schematic
drawings for the binding of Glu (A), DCG-IV (B), 1S,3S-ACPD (C),
1S,3R-ACPD (D), and 2R,4R-APDC (E). Hydrogen atoms attached at
the C[  ]atom of the ligands
are modeled with the corresponding ideal geometries. Only the
residues/water molecules that directly interact with one of the
agonists are drawn. Red and blue lines indicate hydrogen-bonding
and VDW contact, respectively. Either of the two carboxyl oxygen
atoms connected by the green line in B is likely to be
protonated, as suggested from the short distance between them
(2.4 Å).
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Figure 4.
Fig. 4. The ligand-binding pocket. (A) Conserved amino acid
residues involved in ligand binding. Red, green, and blue stick
models represent the structures for mGluR-I[1], mGluR-II[3], and
mGluR-III[7], respectively. The three closed protomers were
superimposed by least-square fitting. The model of the closed
mGluR-III[7] was constructed as described in the text. (B)
Difference in the open angle of the closed protomer between
mGluR-I[1] (purple) and mGluR-II[3] (green). The yellow stick
model represents the bound Glu. The black arrow indicates the
view direction in A. (C–E) The ligand-binding pockets of
mGluR-I[1] (C), mGluR-II[3] (D), and mGluR-III[7] (E) as viewed
in A. Each molecular model is colored as in Fig. 1B. Red lines
indicate the conserved surface shown in A. (F) Diagram
representing the DCG-IV binding of mGluR-II[3], viewed from
directions similar to that in A. The structure of the closed
protomers of mGluR-I[1] (green) (4) is superimposed onto the
mGluR-II[3]structures (yellow).
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