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* Residue conservation analysis
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PDB id:
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Complex (isomerase/protein kinase)
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Title:
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Crystal structure of the cytoplasmic domain of the type i tgf-beta receptor in complex with fkbp12
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Structure:
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Fk506-binding protein. Chain: a, c, e, g. Synonym: fkbp12. Engineered: yes. Tgf-b superfamily receptor type i. Chain: b, d, f, h. Fragment: cytoplasmic portion. Synonym: serine/threonine-protein kinase receptor r4. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Cell_line: plys s. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: sf9. Expressed in: escherichia coli. Expression_system_taxid: 562.
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Biol. unit:
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Dimer (from
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Resolution:
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2.60Å
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R-factor:
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0.249
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R-free:
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0.269
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Authors:
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M.Huse,Y.-G.Chen,J.Massague,J.Kuriyan
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Key ref:
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M.Huse
et al.
(1999).
Crystal structure of the cytoplasmic domain of the type I TGF beta receptor in complex with FKBP12.
Cell,
96,
425-436.
PubMed id:
DOI:
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Date:
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13-Jan-99
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Release date:
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15-Jun-99
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PROCHECK
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Headers
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References
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Enzyme class 1:
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Chains A, C, E, G:
E.C.5.2.1.8
- peptidylprolyl isomerase.
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Reaction:
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[protein]-peptidylproline (omega=180) = [protein]-peptidylproline (omega=0)
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Peptidylproline (omega=180)
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=
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peptidylproline (omega=0)
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Enzyme class 2:
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Chains B, D, F, H:
E.C.2.7.11.30
- receptor protein serine/threonine kinase.
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Reaction:
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1.
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L-seryl-[receptor-protein] + ATP = O-phospho-L-seryl-[receptor- protein] + ADP + H+
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2.
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L-threonyl-[receptor-protein] + ATP = O-phospho-L-threonyl-[receptor- protein] + ADP + H+
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L-seryl-[receptor-protein]
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+
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ATP
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=
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O-phospho-L-seryl-[receptor- protein]
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+
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ADP
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+
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H(+)
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L-threonyl-[receptor-protein]
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+
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ATP
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=
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O-phospho-L-threonyl-[receptor- protein]
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+
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ADP
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+
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H(+)
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Note, where more than one E.C. class is given (as above), each may
correspond to a different protein domain or, in the case of polyprotein
precursors, to a different mature protein.
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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DOI no:
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Cell
96:425-436
(1999)
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PubMed id:
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Crystal structure of the cytoplasmic domain of the type I TGF beta receptor in complex with FKBP12.
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M.Huse,
Y.G.Chen,
J.Massagué,
J.Kuriyan.
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ABSTRACT
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Activation of the type I TGFbeta receptor (TbetaR-I) requires phosphorylation of
a regulatory segment known as the GS region, located upstream of the
serine/threonine kinase domain in the cytoplasmic portion of the receptor. The
crystal structure of a fragment of unphosphorylated TbetaR-I, containing both
the GS region and the catalytic domain, has been determined in complex with the
FK506-binding protein FKBP12. TbetaR-I adopts an inactive conformation that is
maintained by the unphosphorylated GS region. FKBP12 binds to the GS region of
the receptor, capping the TbetaR-II phosphorylation sites and further
stabilizing the inactive conformation of TbetaR-I. Certain structural features
at the catalytic center of TbetaR-I are characteristic of tyrosine kinases
rather than Ser/Thr kinases.
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Selected figure(s)
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Figure 4.
Figure 4. The Inhibited Conformation of T β R-I Is
Maintained by the GS Region and the Activation Segment(A) A
ribbon drawing showing the hydrophobic interactions made between
the GS region helices and the top of the kinase β sheet. T β
R-I is viewed from above the kinase N lobe. Thr-204, the site of
a constitutively activating T β R-I mutation ([55]), is
indicated.(B) A ribbon drawing of the complex showing
interactions between the GS loop and the T β R-I kinase, as
well as contacts formed between FKBP12 and T β R-I. Several
interacting residues are shown, with hydrogen bonding indicated
by dashed purple bonds. The L45 loop is indicated.(C) T β R-I
viewed from an oblique angle above the kinase N lobe. The T β
R-II phosphorylation sites are indicated, as are several
residues involved in ionic or polar interactions that stabilize
the placement of the C helix. The movement of the C helix and
the N lobe β sheet into an active conformation appears to be
blocked by the GS loop and a short stretch within the activation
segment. These two steric blockers have been colored magenta.(D)
The same view as in (C), with a molecular surface representation
of the kinase C lobe. The α C side chains have been included to
indicate the space occupied by the helix. The outward rotation
of the C helix and the N lobe β sheet is blocked by the barrier
created by the activation segment.
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Figure 5.
Figure 5. A Comparison of the FKBP12–FK506 and FKBP12–T
β R-I ComplexesA surface representation of FKBP12 bound to
FK506 is shown to the left ([57]). To the right is shown a
surface representation of FKBP12 bound to the T β R-I GS
region. Leu-195 and Leu-196 are bound in the same hydrophobic
pocket used to engage immunosuppressant.
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The above figures are
reprinted
by permission from Cell Press:
Cell
(1999,
96,
425-436)
copyright 1999.
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Figures were
selected
by an automated process.
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Literature references that cite this PDB file's key reference
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Google scholar
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PubMed id
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Reference
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| |
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and
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(2010).
Cyclophilin B as a co-regulator of prolactin-induced gene expression and function in breast cancer cells.
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J Mol Endocrinol,
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| |
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PDB code:
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PDB codes:
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Nat Methods,
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Interaction of FKBP12.6 with the cardiac ryanodine receptor C-terminal domain.
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J Biol Chem,
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J Biol Chem,
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The structural basis for autoinhibition of FLT3 by the juxtamembrane domain.
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Mol Cell,
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PDB code:
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M.de Caestecker
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The transforming growth factor-beta superfamily of receptors.
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Mol Microbiol,
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Biophys J,
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PDB codes:
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The BMP7/ActRII extracellular domain complex provides new insights into the cooperative nature of receptor assembly.
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Mol Cell,
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PDB codes:
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J.P.Himanen,
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X-ray crystal structure and functional analysis of vaccinia virus K3L reveals molecular determinants for PKR subversion and substrate recognition.
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Mol Cell,
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PDB code:
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A.Mehra,
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Genes Dev,
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PDB codes:
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D.S.Horowitz,
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EMBO J,
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Structure,
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PDB code:
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K.N.Brazin,
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Cell,
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Crystal structure of a phosphorylated Smad2. Recognition of phosphoserine by the MH2 domain and insights on Smad function in TGF-beta signaling.
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Mol Cell,
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PDB code:
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J.Yue,
and
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Cell,
106,
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PDB code:
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M.A.Shogren-Knaak,
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Mol Cell,
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PDB code:
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PDB code:
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
code is
shown on the right.
|
 |
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