PDBsum entry 1rhf

Transferase

PDB id: 1rhf

Contents

Protein chains

176 a.a. *

Ligands

ACT ×4

EPE

Metals

_ZN

Waters ×275

* Residue conservation analysis

PDB id:

1rhf

Name:

Transferase

Title:

Crystal structure of human tyro3-d1d2

Structure:

Tyrosine-protein kinase receptor tyro3. Chain: a, b. Fragment: n-terminal ig-domain. Synonym: tyrosine-protein kinase rse, tyrosine-protein kinase sky, tyrosine-protein kinase dtk, protein-tyrosine kinase byk. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: tyro3, rse, sky, dtk, byk. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.96Å R-factor: 0.213 R-free: 0.256

Authors:

C.Heiring,B.Dahlback,Y.A.Muller

Key ref:

C.Heiring et al. (2004). Ligand recognition and homophilic interactions in Tyro3: structural insights into the Axl/Tyro3 receptor tyrosine kinase family. J Biol Chem, 279, 6952-6958. PubMed id: 14623883 DOI: 10.1074/jbc.M311750200

Date:

14-Nov-03 Release date: 23-Mar-04

Protein chains

Q06418  (TYRO3_HUMAN) -  Tyrosine-protein kinase receptor TYRO3 from Homo sapiens

Seq: 890 a.a.

Struc: 176 a.a.

Enzyme reactions

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

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

Added reference

DOI no: 10.1074/jbc.M311750200

J Biol Chem 279:6952-6958 (2004)

PubMed id: 14623883

Ligand recognition and homophilic interactions in Tyro3: structural insights into the Axl/Tyro3 receptor tyrosine kinase family.

C.Heiring, B.Dahlbäck, Y.A.Muller.

ABSTRACT

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.

Selected figure(s)

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.

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.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2004, 279, 6952-6958) copyright 2004.

Figures were selected by an automated process.