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PDBsum entry 1h30

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protein ligands metals links
Laminin g-domain protein PDB id
1h30
Jmol PyMol
Contents
Protein chain
391 a.a. *
Ligands
SO4 ×2
Metals
_CA
Waters ×122
* Residue conservation analysis
PDB id:
1h30
Name: Laminin g-domain protein
Title: C-terminal lg domain pair of human gas6
Structure: Growth-arrest-specific protein. Chain: a. Fragment: c-terminal lg domain pair, residues 261-678. Synonym: gas6. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: 293-ebna.
Biol. unit: Monomer (from PDB file)
Resolution:
2.2Å     R-factor:   0.234     R-free:   0.259
Authors: T.Sasaki,P.G.Knyazev,Y.Cheburkin,W.Gohring,D.Tisi,A.Ullrich, R.Timpl,E.Hohenester
Key ref:
T.Sasaki et al. (2002). Crystal structure of a C-terminal fragment of growth arrest-specific protein Gas6. Receptor tyrosine kinase activation by laminin G-like domains. J Biol Chem, 277, 44164-44170. PubMed id: 12218057 DOI: 10.1074/jbc.M207340200
Date:
21-Aug-02     Release date:   30-Jan-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q14393  (GAS6_HUMAN) -  Growth arrest-specific protein 6
Seq:
Struc:
 
Seq:
Struc:
721 a.a.
391 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 

 
DOI no: 10.1074/jbc.M207340200 J Biol Chem 277:44164-44170 (2002)
PubMed id: 12218057  
 
 
Crystal structure of a C-terminal fragment of growth arrest-specific protein Gas6. Receptor tyrosine kinase activation by laminin G-like domains.
T.Sasaki, P.G.Knyazev, Y.Cheburkin, W.Göhring, D.Tisi, A.Ullrich, R.Timpl, E.Hohenester.
 
  ABSTRACT  
 
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.
 
  Selected figure(s)  
 
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.
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.
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2002, 277, 44164-44170) copyright 2002.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20958312 G.Lemke, and T.Burstyn-Cohen (2010).
TAM receptors and the clearance of apoptotic cells.
  Ann N Y Acad Sci, 1209, 23-29.  
  21057587 L.Qingxian, L.Qiutang, and L.Qingjun (2010).
Regulation of phagocytosis by TAM receptors and their ligands.
  Front Biol, 5, 227-237.  
19244162 M.J.Heeb, D.Prashun, J.H.Griffin, and B.N.Bouma (2009).
Plasma protein S contains zinc essential for efficient activated protein C-independent anticoagulant activity and binding to factor Xa, but not for efficient binding to tissue factor pathway inhibitor.
  FASEB J, 23, 2244-2253.  
18785927 G.Johnson, C.Swart, and S.W.Moore (2008).
Non-enzymatic developmental functions of acetylcholinesterase--the question of redundancy.
  FEBS J, 275, 5129-5138.  
18421305 G.Lemke, and C.V.Rothlin (2008).
Immunobiology of the TAM receptors.
  Nat Rev Immunol, 8, 327-336.  
16939220 K.E.Persson, J.Stenflo, S.Linse, Y.Stenberg, R.J.Preston, D.A.Lane, and S.M.Rezende (2006).
Binding of calcium to anticoagulant protein S: role of the fourth EGF module.
  Biochemistry, 45, 10682-10689.  
16444701 S.Beug, S.G.Vascotto, and C.Tsilfidis (2006).
Newt orthologue of Growth arrest-specific 6 (NvGas6) is implicated in stress response during newt forelimb regeneration.
  Dev Dyn, 235, 711-722.  
17064312 S.Hafizi, and B.Dahlbäck (2006).
Gas6 and protein S. Vitamin K-dependent ligands for the Axl receptor tyrosine kinase subfamily.
  FEBS J, 273, 5231-5244.  
16362042 T.Sasaki, P.G.Knyazev, N.J.Clout, Y.Cheburkin, W.Göhring, A.Ullrich, R.Timpl, and E.Hohenester (2006).
Structural basis for Gas6-Axl signalling.
  EMBO J, 25, 80-87.
PDB code: 2c5d
  15650770 A.Angelillo-Scherrer, L.Burnier, N.Flores, P.Savi, M.DeMol, P.Schaeffer, J.M.Herbert, G.Lemke, S.P.Goff, G.K.Matsushima, H.S.Earp, C.Vesin, M.F.Hoylaerts, S.Plaisance, D.Collen, E.M.Conway, B.Wehrle-Haller, and P.Carmeliet (2005).
Role of Gas6 receptors in platelet signaling during thrombus stabilization and implications for antithrombotic therapy.
  J Clin Invest, 115, 237-246.  
15930001 A.Fallahi, B.Kroll, L.R.Warner, R.J.Oxford, K.M.Irwin, L.M.Mercer, S.E.Shadle, and J.T.Oxford (2005).
Structural model of the amino propeptide of collagen XI alpha1 chain with similarity to the LNS domains.
  Protein Sci, 14, 1526-1537.  
16359517 I.Hasanbasic, I.Rajotte, and M.Blostein (2005).
The role of gamma-carboxylation in the anti-apoptotic function of gas6.
  J Thromb Haemost, 3, 2790-2797.  
16023350 J.Stetefeld, and M.A.Ruegg (2005).
Structural and functional diversity generated by alternative mRNA splicing.
  Trends Biochem Sci, 30, 515-521.  
15733062 W.R.Gould, S.M.Baxi, R.Schroeder, Y.W.Peng, R.J.Leadley, J.T.Peterson, and L.A.Perrin (2005).
Gas6 receptors Axl, Sky and Mer enhance platelet activation and regulate thrombotic responses.
  J Thromb Haemost, 3, 733-741.  
15016366 J.Stetefeld, A.T.Alexandrescu, M.W.Maciejewski, M.Jenny, K.Rathgeb-Szabo, T.Schulthess, R.Landwehr, S.Frank, M.A.Ruegg, and R.A.Kammerer (2004).
Modulation of agrin function by alternative splicing and Ca2+ binding.
  Structure, 12, 503-515.
PDB codes: 1pz7 1pz8 1pz9 1q56
15108283 X.Muñoz, L.Sumoy, R.Ramírez-Lorca, J.Villar, P.G.de Frutos, and N.Sala (2004).
Human vitamin K-dependent GAS6: gene structure, allelic variation, and association with stroke.
  Hum Mutat, 23, 506-512.  
12871288 B.Dahlbäck, and B.O.Villoutreix (2003).
Molecular recognition in the protein C anticoagulant pathway.
  J Thromb Haemost, 1, 1525-1534.  
14732928 R.L.Rich, and D.G.Myszka (2003).
A survey of the year 2002 commercial optical biosensor literature.
  J Mol Recognit, 16, 351-382.  
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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