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214 a.a.
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214 a.a.
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200 a.a.
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* Residue conservation analysis
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PDB id:
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Complex (immunoglobulin/tissue factor)
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Title:
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A complex of extracellular domain of tissue factor with an inhibitory fab (5g9)
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Structure:
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Immunoglobulin fab 5g9 (light chain). Chain: a, d. Fragment: light chain residues 1 - 214. Synonym: fab, fab light chain, fab heavy chain. Immunoglobulin fab 5g9 (heavy chain). Chain: b, e. Fragment: heavy chain residues 1 - 214. Synonym: fab, fab light chain, fab heavy chain. Tissue factor.
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Source:
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Mus musculus. House mouse. Organism_taxid: 10090. Cell_line: bl21. Organ: blood. Tissue: blood. Homo sapiens. Human. Organism_taxid: 9606.
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Biol. unit:
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Trimer (from
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Resolution:
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3.00Å
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R-factor:
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0.217
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R-free:
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0.285
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Authors:
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M.Huang,R.Syed,E.A.Stura,M.J.Stone,R.S.Stefanko,W.Ruf, T.S.Edgington,I.A.Wilson
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Key ref:
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M.Huang
et al.
(1998).
The mechanism of an inhibitory antibody on TF-initiated blood coagulation revealed by the crystal structures of human tissue factor, Fab 5G9 and TF.G9 complex.
J Mol Biol,
275,
873-894.
PubMed id:
DOI:
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Date:
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10-Apr-97
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Release date:
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25-Feb-98
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PROCHECK
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Headers
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References
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No UniProt id for this chain
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Gene Ontology (GO) functional annotation
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Cellular component
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integral to membrane
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1 term
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Biological process
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blood coagulation
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1 term
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Biochemical function
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protein binding
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1 term
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DOI no:
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J Mol Biol
275:873-894
(1998)
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PubMed id:
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The mechanism of an inhibitory antibody on TF-initiated blood coagulation revealed by the crystal structures of human tissue factor, Fab 5G9 and TF.G9 complex.
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M.Huang,
R.Syed,
E.A.Stura,
M.J.Stone,
R.S.Stefanko,
W.Ruf,
T.S.Edgington,
I.A.Wilson.
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ABSTRACT
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The tissue factor (TF)-initiated blood coagulation protease cascade can be
greatly inhibited in vivo by a potent anti-human-TF monoclonal antibody, 5G9.
This antibody binds the carboxyl module of the extracellular domain of TF with a
nanomolar binding constant and inhibits the formation of the TF.VIIa.X ternary
initiation complex. We have determined the crystal structures of the
extra-cellular modules of human TF, Fab 5G9, and their complex (TF.5G9) to 2.4
A, 2. 5 A, and 3.0 A, respectively, and measured the apparent inhibition
constants of 5G9 on a panel of TF mutants. In our unliganded TF structure, a 7
degrees change in the relative orientation between the D1 and D2 modules was
observed when compared with other published TF structures. Comparison of the
free and bound Fab 5G9 indicates that small segmental and side chain variation
of the antibody complementarity determining regions occurred on complexation
with TF. The antibody-antigen recognition involves 18 TF antigen residues and 19
Fab residues from six CDR with one of the largest buried surface areas seen to
date. A combination of structural and mutagenesis data indicate that Tyr156,
Lys169, Arg200, and Lys201 play the major role in the antibody recognition. The
TF. 5G9 structure provides insights into the mechanism by which the antibody 5G9
inhibits formation of the TF.VIIa.X ternary complex.
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Selected figure(s)
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Figure 6.
Figure 6. Interactions in the TF·5G9 interface. Top
stereoview shows the overall orientation and the interaction
between some β-strands (labeled in green) of the D2 module of
TF (green) with the CDRs of Fab 5G9 (blue and pale blue for
heavy and light chains); bottom stereoview shows all 15 hydrogen
bonds (Table 5) and all residues (labeled in black for Fab 5G9
and green for TF) involved in the TF-5G9 interaction (Table 3).
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Figure 10.
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(1998,
275,
873-894)
copyright 1998.
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Figures were
selected
by the author.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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E.Karaca,
and
A.M.Bonvin
(2011).
A multidomain flexible docking approach to deal with large conformational changes in the modeling of biomolecular complexes.
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Structure, 19,
555-565.
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A.Malik,
A.Firoz,
V.Jha,
E.Sunderasan,
and
S.Ahmad
(2010).
Modeling the three-dimensional structures of an unbound single-chain variable fragment (scFv) and its hypothetical complex with a Corynespora cassiicola toxin, cassiicolin.
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J Mol Model, 16,
1883-1893.
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J.A.Jiao,
A.B.Kelly,
U.M.Marzec,
E.Nieves,
J.Acevedo,
M.Burkhardt,
A.Edwards,
X.Y.Zhu,
P.A.Chavaillaz,
A.Wong,
J.L.Wong,
J.O.Egan,
D.Taylor,
P.R.Rhode,
and
H.C.Wong
(2010).
Inhibition of acute vascular thrombosis in chimpanzees by an anti-human tissue factor antibody targeting the factor X binding site.
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Thromb Haemost, 103,
224-233.
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R.Ganesan,
C.Eigenbrot,
and
D.Kirchhofer
(2010).
Structural and mechanistic insight into how antibodies inhibit serine proteases.
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Biochem J, 430,
179-189.
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C.E.Leysath,
A.F.Monzingo,
J.A.Maynard,
J.Barnett,
G.Georgiou,
B.L.Iverson,
and
J.D.Robertus
(2009).
Crystal structure of the engineered neutralizing antibody M18 complexed to domain 4 of the anthrax protective antigen.
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J Mol Biol, 387,
680-693.
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PDB codes:
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C.J.Farady,
P.F.Egea,
E.L.Schneider,
M.R.Darragh,
and
C.S.Craik
(2008).
Structure of an Fab-protease complex reveals a highly specific non-canonical mechanism of inhibition.
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J Mol Biol, 380,
351-360.
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PDB code:
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C.Li,
M.E.Collier,
G.A.Frentzou,
J.Greenman,
and
C.Ettelaie
(2008).
Investigation of the mechanisms of tissue factor-mediated evasion of tumour cells from cellular cytotoxicity.
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Cancer Immunol Immunother, 57,
1347-1355.
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J.E.Lee,
A.Kuehne,
D.M.Abelson,
M.L.Fusco,
M.K.Hart,
and
E.O.Saphire
(2008).
Complex of a protective antibody with its Ebola virus GP peptide epitope: unusual features of a V lambda x light chain.
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J Mol Biol, 375,
202-216.
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PDB code:
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N.Mackman
(2008).
Tissue-specific hemostasis: role of tissue factor.
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J Thromb Haemost, 6,
303-305.
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V.Moreau,
C.Fleury,
D.Piquer,
C.Nguyen,
N.Novali,
S.Villard,
D.Laune,
C.Granier,
and
F.Molina
(2008).
PEPOP: computational design of immunogenic peptides.
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BMC Bioinformatics, 9,
71.
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Y.C.Kim,
and
G.Hummer
(2008).
Coarse-grained models for simulations of multiprotein complexes: application to ubiquitin binding.
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J Mol Biol, 375,
1416-1433.
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H.H.Versteeg,
and
W.Ruf
(2007).
Tissue factor coagulant function is enhanced by protein-disulfide isomerase independent of oxidoreductase activity.
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J Biol Chem, 282,
25416-25424.
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M.Hoffman,
C.M.Colina,
A.G.McDonald,
G.M.Arepally,
L.Pedersen,
and
D.M.Monroe
(2007).
Tissue factor around dermal vessels has bound factor VII in the absence of injury.
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J Thromb Haemost, 5,
1403-1408.
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P.Scheerer,
A.Kramer,
L.Otte,
M.Seifert,
H.Wessner,
C.Scholz,
N.Krauss,
J.Schneider-Mergener,
and
W.Höhne
(2007).
Structure of an anti-cholera toxin antibody Fab in complex with an epitope-derived D-peptide: a case of polyspecific recognition.
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J Mol Recognit, 20,
263-274.
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PDB code:
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J.Ahamed,
H.H.Versteeg,
M.Kerver,
V.M.Chen,
B.M.Mueller,
P.J.Hogg,
and
W.Ruf
(2006).
Disulfide isomerization switches tissue factor from coagulation to cell signaling.
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Proc Natl Acad Sci U S A, 103,
13932-13937.
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S.P.Bajaj,
A.E.Schmidt,
S.Agah,
M.S.Bajaj,
and
K.Padmanabhan
(2006).
High resolution structures of p-aminobenzamidine- and benzamidine-VIIa/soluble tissue factor: unpredicted conformation of the 192-193 peptide bond and mapping of Ca2+, Mg2+, Na+, and Zn2+ sites in factor VIIa.
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J Biol Chem, 281,
24873-24888.
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PDB codes:
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D.Segal,
and
M.Eisenstein
(2005).
The effect of resolution-dependent global shape modifications on rigid-body protein-protein docking.
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Proteins, 59,
580-591.
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A.Berchanski,
B.Shapira,
and
M.Eisenstein
(2004).
Hydrophobic complementarity in protein-protein docking.
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Proteins, 56,
130-142.
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A.Dorfleutner,
E.Hintermann,
T.Tarui,
Y.Takada,
and
W.Ruf
(2004).
Cross-talk of integrin alpha3beta1 and tissue factor in cell migration.
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Mol Biol Cell, 15,
4416-4425.
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J.H.Morrissey
(2004).
Tissue factor: a key molecule in hemostatic and nonhemostatic systems.
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Int J Hematol, 79,
103-108.
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M.Huang,
B.C.Furie,
and
B.Furie
(2004).
Crystal structure of the calcium-stabilized human factor IX Gla domain bound to a conformation-specific anti-factor IX antibody.
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J Biol Chem, 279,
14338-14346.
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PDB code:
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R.Pawlinski,
B.Pedersen,
G.Schabbauer,
M.Tencati,
T.Holscher,
W.Boisvert,
P.Andrade-Gordon,
R.D.Frank,
and
N.Mackman
(2004).
Role of tissue factor and protease-activated receptors in a mouse model of endotoxemia.
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Blood, 103,
1342-1347.
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B.Ma,
M.Shatsky,
H.J.Wolfson,
and
R.Nussinov
(2002).
Multiple diverse ligands binding at a single protein site: a matter of pre-existing populations.
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Protein Sci, 11,
184-197.
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K.E.Persson,
B.O.Villoutreix,
A.M.Thämlitz,
K.E.Knobe,
and
J.Stenflo
(2002).
The N-terminal epidermal growth factor-like domain of coagulation factor IX. Probing its functions in the activation of factor IX and factor X with a monoclonal antibody.
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J Biol Chem, 277,
35616-35624.
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D.Kirchhofer,
C.Eigenbrot,
M.T.Lipari,
P.Moran,
M.Peek,
and
R.F.Kelley
(2001).
The tissue factor region that interacts with factor Xa in the activation of factor VII.
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Biochemistry, 40,
675-682.
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S.Monaco-Malbet,
C.Berthet-Colominas,
A.Novelli,
N.Battaï,
N.Piga,
V.Cheynet,
F.Mallet,
and
S.Cusack
(2000).
Mutual conformational adaptations in antigen and antibody upon complex formation between an Fab and HIV-1 capsid protein p24.
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Structure, 8,
1069-1077.
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PDB codes:
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Y.Li,
H.Li,
S.J.Smith-Gill,
and
R.A.Mariuzza
(2000).
Three-dimensional structures of the free and antigen-bound Fab from monoclonal antilysozyme antibody HyHEL-63(,).
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Biochemistry, 39,
6296-6309.
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PDB codes:
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B.Selisko,
A.F.Licea,
B.Becerril,
F.Zamudio,
L.D.Possani,
and
E.Horjales
(1999).
Antibody BCF2 against scorpion toxin Cn2 from Centuroides noxius Hoffmann: primary structure and three-dimensional model as free Fv fragment and complexed with its antigen.
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Proteins, 37,
130-143.
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J.Shobe,
C.D.Dickinson,
T.S.Edgington,
and
W.Ruf
(1999).
Macromolecular substrate affinity for the tissue factor-factor VIIa complex is independent of scissile bond docking.
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J Biol Chem, 274,
24171-24175.
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K.C.Garcia,
L.Teyton,
and
I.A.Wilson
(1999).
Structural basis of T cell recognition.
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Annu Rev Immunol, 17,
369-397.
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O.Livnah,
E.A.Stura,
S.A.Middleton,
D.L.Johnson,
L.K.Jolliffe,
and
I.A.Wilson
(1999).
Crystallographic evidence for preformed dimers of erythropoietin receptor before ligand activation.
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Science, 283,
987-990.
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PDB code:
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Y.A.Muller,
R.F.Kelley,
and
A.M.de Vos
(1998).
Hinge bending within the cytokine receptor superfamily revealed by the 2.4 A crystal structure of the extracellular domain of rabbit tissue factor.
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Protein Sci, 7,
1106-1115.
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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
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only a partial list as not all journals are covered by
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so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
codes are
shown on the right.
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Links
