PDBsum entry 2c5d

Signaling protein/receptor

PDB id: 2c5d

Contents

Protein chains

381 a.a. *

192 a.a. *

Ligands

NAG-NAG ×2

SO4

Metals

_CA ×2

_NI ×2

* Residue conservation analysis

PDB id:

2c5d

Name:

Signaling protein/receptor

Title:

Structure of a minimal gas6-axl complex

Structure:

Growth-arrest-specific protein 6 precursor. Chain: a, b. Fragment: lg domains, residues 207-624. Synonym: gas-6. Engineered: yes. Tyrosine-protein kinase receptor ufo. Chain: c, d. Fragment: ig domains, residues 26-220. Synonym: axl oncogene.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: 293-ebna. Expressed in: escherichia coli. Expression_system_taxid: 511693.

Biol. unit:

Tetramer (from PDB file)

Resolution:

3.30Å R-factor: 0.241 R-free: 0.265

Authors:

T.Sasaki,P.G.Knyazev,N.J.Clout,Y.Cheburkin,W.Goehring,A.Ullrich, R.Timpl,E.Hohenester

Key ref:

T.Sasaki et al. (2006). Structural basis for Gas6-Axl signalling. EMBO J, 25, 80-87. PubMed id: 16362042 DOI: 10.1038/sj.emboj.7600912

Date:

26-Oct-05 Release date: 19-Dec-05

Protein chains

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

Seq: 678 a.a.

Struc: 381 a.a.

Protein chains

P30530  (UFO_HUMAN) -  Tyrosine-protein kinase receptor UFO from Homo sapiens

Seq: 894 a.a.

Struc: 192 a.a.

Enzyme reactions

• Enzyme class: Chains C, D: E.C.2.7.10.1 - receptor protein-tyrosine kinase.
• Reaction: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H⁺

L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] (Bound ligand (Het Group name = NAG) matches with 41.38% similarity) + ADP + H(+)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

DOI no: 10.1038/sj.emboj.7600912

EMBO J 25:80-87 (2006)

PubMed id: 16362042

Structural basis for Gas6-Axl signalling.

T.Sasaki, P.G.Knyazev, N.J.Clout, Y.Cheburkin, W.Göhring, A.Ullrich, R.Timpl, E.Hohenester.

ABSTRACT

Receptor tyrosine kinases of the Axl family are activated by the vitamin K-dependent protein Gas6. Axl signalling plays important roles in cancer, spermatogenesis, immunity, and platelet function. The crystal structure at 3.3 A resolution of a minimal human Gas6/Axl complex reveals an assembly of 2:2 stoichiometry, in which the two immunoglobulin-like domains of the Axl ectodomain are crosslinked by the first laminin G-like domain of Gas6, with no direct Axl/Axl or Gas6/Gas6 contacts. There are two distinct Gas6/Axl contacts of very different size, both featuring interactions between edge beta-strands. Structure-based mutagenesis, protein binding assays and receptor activation experiments demonstrate that both the major and minor Gas6 binding sites are required for productive transmembrane signalling. Gas6-mediated Axl dimerisation is likely to occur in two steps, with a high-affinity 1:1 Gas6/Axl complex forming first. Only the minor Gas6 binding site is highly conserved in the other Axl family receptors, Sky/Tyro3 and Mer. Specificity at the major contact is suggested to result from the segregation of charged and apolar residues to opposite faces of the newly formed beta-sheet.

Selected figure(s)

Figure 1.
Figure 1 Overall architecture of the Gas6-LG/Axl-IG complex. Shown are three orthogonal views. (A) Top view, towards the cell membrane harbouring the receptor. (B) Side view, with the cell membrane at the bottom. (C) Front view, in the direction indicated by the arrow in (B). Surface representations are shown in (A) and (B), while a cartoon representation is shown in (C). Gas6-LG is in cyan (N-terminal segment and LG1) and green (LG2), Axl-IG is in yellow (IG1) and brown (IG2). In (C), the Gas6-LG molecule at the back has been removed for clarity, a calcium ion in the LG1-LG2 interface is shown as a pink sphere, and the Gas6/Axl contact sites are labelled.

Figure 3.
Figure 3 Detailed structure of the Gas6/Axl contact sites. (A) Front view of the major contact, in a direction similar to Figure 1C, showing the polar -sheet surface. (B) Back view of the major contact, showing the apolar -sheet surface. (C) Front view of the minor contact. Main chain traces are shown in the colours used in Figure 1. Selected interface residues are shown as sticks. The two N-acetylglucosamine moities attached to Asn420^Gas6 are shown in pink. Hydrogen bonds are shown as broken lines. Main-chain hydrogen bonds between -strands have been omitted for clarity.

The above figures are reprinted by permission from Macmillan Publishers Ltd: EMBO J (2006, 25, 80-87) copyright 2006.

Figures were selected by an automated process.