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PDBsum entry 1s1c
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Signaling protein
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PDB id
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1s1c
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Structural insights into the interaction of rocki with the switch regions of rhoa.
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Authors
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R.Dvorsky,
L.Blumenstein,
I.R.Vetter,
M.R.Ahmadian.
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Ref.
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J Biol Chem, 2004,
279,
7098-7104.
[DOI no: ]
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PubMed id
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Abstract
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The Rho-ROCK pathway modulates the phosphorylation level of a variety of
important signaling proteins and is thereby involved in miscellaneous cellular
processes including cell migration, neurite outgrowth, and smooth muscle
contraction. The observation of the involvement of the Rho-ROCK pathway in tumor
invasion and in diseases such as hypertension and bronchial asthma makes it an
interesting target for drug development. We herein present the crystal structure
of the complex between active RhoA and the Rho-binding domain of ROCKI. The
Rho-binding domain structure forms a parallel alpha-helical coiled-coil dimer
and, in contrast to the published Rho-protein kinase N structure, binds
exclusively to the switch I and II regions of the guanosine
5'-(beta,gamma-imido)triphosphate-bound RhoA. The switch regions of two
different RhoA molecules form a predominantly hydrophobic patch, which is
complementarily bound by two identical short helices of 13 residues (amino acids
998-1010). The identified ROCK-binding site of RhoA strikingly supports the
assumption of a common consensus-binding site for effector recognition.
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Figure 3.
FIG. 3. Determinants of the ROCK specificity toward Rho. A,
stereoview of superimposed structures of RhoA (orange) (33),
Rac1 (yellow) (50), and Cdc42 (brown) (51), focusing on the
ROCK-binding region of RhoA. Amino acids are labeled according
to the standard numbering of RhoA. B, surface representation of
the GTPases in the same orientation as in A. The residues that
interact with ROCKI-RBD are colored as follows: blue, positively
charged nitrogen atoms; red, negatively charged oxygen atoms;
green, non-charged hydrophobic atoms; black, the oxygen atom of
Tyr-66. Phe-39, found to be crucial for the specificity toward
ROCKI, is shown in yellow.
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Figure 4.
FIG. 4. ROCK and PKN contact sites of RhoA. The contact
site I proposed as the main contact site of RhoA with PKN (27)
is colored in brown. The common binding site of RhoA for both
ROCKI and PKN (contact site II) is highlighted in orange. The
sites interacting exclusively with PKN and ROCK are colored in
yellow and red, respectively. All of the contact sites were
determined using the 4.5-Å threshold.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2004,
279,
7098-7104)
copyright 2004.
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