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PDBsum entry 2dfk
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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 crystal structure of cdc42 in complex with collybistin ii, A gephyrin-Interacting guanine nucleotide exchange factor.
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Authors
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S.Xiang,
E.Y.Kim,
J.J.Connelly,
N.Nassar,
J.Kirsch,
J.Winking,
G.Schwarz,
H.Schindelin.
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Ref.
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J Mol Biol, 2006,
359,
35-46.
[DOI no: ]
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PubMed id
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Abstract
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The synaptic localization of ion channel receptors is essential for efficient
synaptic transmission and the precise regulation of diverse neuronal functions.
In the central nervous system, ion channel receptors reside in the postsynaptic
membrane where they are juxtaposed to presynaptic terminals. For proper
function, these ion channels have to be anchored to the cytoskeleton, and in the
case of the inhibitory glycine and gamma-amino-butyric acid type A (GABA(A))
receptors this interaction is mediated by a gephyrin centered scaffold.
Highlighting its central role in this receptor anchoring scaffold, gephyrin
interacts with a number of proteins, including the neurospecific guanine
nucleotide exchange factor collybistin. Collybistin belongs to the Dbl family of
guanine nucleotide exchange factors, occurs in multiple splice variants, and is
specific for Cdc42, a small GTPase belonging to the Rho family. The 2.3
Angstroms resolution crystal structure of the Cdc42-collybistin II complex
reveals a novel conformation of the switch I region of Cdc42. It also provides
the first direct observation of structural changes in the relative orientation
of the Dbl-homology domain and the pleckstrin-homology domain in the same Dbl
family protein. Biochemical data indicate that gephyrin negatively regulates
collybistin activity.
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Figure 4.
Figure 4. Structural changes of the PH domain. (a)
Structural comparison of the tandem DH/PH domains. Collybistin
II, Tiam 1, Dbs, intersectin and Sos1 were aligned according to
the conserved regions of their DH domains. In collybistin II,
the PH domains are colored green in the open conformation and
gray in the closed conformation. (b) Collybistin II in the open
conformation. Residues that lose solvent-accessible surface area
upon transition to the closed conformation are highlighted with
positively charged residues in blue, negatively charged residues
in red, polar residues in cyan and non-polar residues in gray.
(c) Collybistin II in the closed conformation (same color code).
An additional salt-bridge between Asp136 (red) and Lys379 (blue)
in the closed conformation is visible on the bottom of the DH/PH
domain interface. (b) and (c) are aligned according to their PH
domains. Residues highlighted in (b) with an arrow are
disordered in the open conformation.
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Figure 5.
Figure 5. Membrane interaction model of the
Cdc42-collybistin II complex. (a) The electrostatic potential of
the open conformation of the Cdc42-collybistin II complex,
calculated at zero ionic strength and contoured at 1.5 kT (blue)
and -1.5 kT (red). (b) Model of the interaction between the
plasma membrane and the complex in the open conformation. The
observed conformation of the Cdc42 C terminus is colored in
cyan, whereas the physiologically relevant conformations present
in the Cdc42-Dbs and Cdc42-GDI complexes are colored in gray and
red, respectively.
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(2006,
359,
35-46)
copyright 2006.
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