PDBsum entry 1h30

Laminin g-domain protein

PDB id: 1h30

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:

2.20Å 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

Protein chain

Q14393  (GAS6_HUMAN) -  Growth arrest-specific protein 6 from Homo sapiens

Seq: 678 a.a.

Struc: 391 a.a.

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.