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PDBsum entry 1rhf
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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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Ligand recognition and homophilic interactions in tyro3: structural insights into the axl/tyro3 receptor tyrosine kinase family.
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Authors
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C.Heiring,
B.Dahlbäck,
Y.A.Muller.
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Ref.
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J Biol Chem, 2004,
279,
6952-6958.
[DOI no: ]
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PubMed id
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Abstract
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The receptor Tyro3 together with Axl and Mer form the Axl/Tyro3 family of
receptor tyrosine kinases. Members of this family play essential roles in
spermatogenesis, immunoregulation, and phagocytosis. Gas6, the product of growth
arrest-specific gene, activates the kinase activity of all three receptors.
Here, we report the first biochemical and structural characterization of a
member of this family, namely of a fragment spanning the two N-terminal Ig
domains of the extracellular part of human Tyro3. Its ligand binding specificity
profile is identical to the activation profile of the native receptor. The
1.95-A crystal structure suggests a common ligand-binding site in this receptor
family located at the interface of the Ig domains and unusually rich in
cis-prolines. Furthermore, both in the crystal and in solution we observed the
ligand-independent dimerization of the receptor fragment. This homophilic
interaction emphasizes previous functional reports, which hinted that in
addition to signal transduction, members of this family of receptors might
participate in cell adhesion.
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Figure 3.
FIG. 3. Structural details in the Tyro3-D1D2 monomer. A,
stereoview of the interface between the first and second Ig
domains of Tyro3-D1D2. Hydrogen bonds are displayed as yellow
dots. The linker segment is shown in an all atom main chain
representation and the remaining parts as C  sketches. The high
number of interactions across the interface suggests a rigid
orientation of the domains. B, stereoview of the
cis-proline-rich BC and C'E loops of the second Ig domain.
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Figure 4.
FIG. 4. Dimer structure and interface of Tyro3-D1D2. A, the
surface representation of the Tyro3-D1D2 dimer (monomers in red
and green) viewed from two different angles shows that
dimerization occurs solely through interactions between the
N-terminal Ig domains (D1). The two monomers are related to each
other by a 2-fold symmetry. B, overview of the dimer interface.
Amino acids involved in the interface are shown as stick
representations in the case of one monomer; in the second
monomer, the corresponding amino acids are shown in a surface
representation and highlighted in dark green when they are part
of the contract surface. C, hydrogen bond network formed between
B-strand residues across the interface.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2004,
279,
6952-6958)
copyright 2004.
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