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PDBsum entry 1h30
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Laminin g-domain protein
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PDB id
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1h30
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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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Crystal structure of a c-Terminal fragment of growth arrest-Specific protein gas6. Receptor tyrosine kinase activation by laminin g-Like domains.
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Authors
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T.Sasaki,
P.G.Knyazev,
Y.Cheburkin,
W.Göhring,
D.Tisi,
A.Ullrich,
R.Timpl,
E.Hohenester.
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Ref.
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J Biol Chem, 2002,
277,
44164-44170.
[DOI no: ]
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PubMed id
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Abstract
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Receptor tyrosine kinases of the Axl family are activated by Gas6, the product
of growth arrest-specific gene 6. Gas6-Axl signaling is implicated in cell
survival, adhesion, and migration. The receptor-binding site of Gas6 is located
within a C-terminal pair of laminin G-like (LG) domains that do not resemble any
other receptor tyrosine kinase ligand. We report the crystal structure at 2.2-A
resolution of a Gas6 fragment spanning both LG domains (Gas6-LG). The structure
reveals a V-shaped arrangement of LG domains strengthened by an interdomain
calcium-binding site. LG2 of Gas6-LG contains two unusual features: an
alpha-helix cradled by one edge of the LG beta-sandwich and a conspicuous patch
of surface-exposed hydrophobic residues. Mutagenesis of some residues in this
patch reduces Gas6-LG binding to the extracellular domain of Axl as well as Axl
activation in glioblastoma cells, identifying a component of the
receptor-binding site of Gas6.
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Figure 2.
Fig. 2. The calcium-binding site in Gas6-LG. The view
direction is similar to that in Fig. 1A. LG1 and LG2 residues
are in cyan and green, respectively, and are labeled. The
calcium ion and two water molecules are shown as pink and red
spheres, respectively. Metal ion-ligand bonds are indicated by
black lines.
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Figure 4.
Fig. 4. The solvent-exposed hydrophobic patch in Gas6-LG.
The Gas6-LG structure is shown as a C trace in
the same orientation as in Fig. 1A. Selected solvent-accessible
hydrophobic residues are shown in atomic detail and are labeled.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2002,
277,
44164-44170)
copyright 2002.
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Secondary reference #1
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Title
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Characterization of gas6, A member of the superfamily of g domain-Containing proteins, As a ligand for rse and axl.
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Authors
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M.R.Mark,
J.Chen,
R.G.Hammonds,
M.Sadick,
P.J.Godowsk.
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Ref.
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J Biol Chem, 1996,
271,
9785-9789.
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PubMed id
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