PDBsum entry 4qt8

Hydrolase/signaling protein

PDB id: 4qt8

Contents

Protein chains

629 a.a.

231 a.a.

Ligands

NAG-NAG-BMA

NAG-NAG

PDB id:

4qt8

Name:

Hydrolase/signaling protein

Title:

Crystal structure of ron sema-psi-ipt1 extracellular domains in complex with msp beta-chain

Structure:

Macrophage-stimulating protein receptor. Chain: b, a. Fragment: extracellular sema-psi-ipt1 domains (unp residues 25-683). Synonym: msp receptor, cdw136, protein-tyrosine kinase 8, p185-ron, ron receptor tyrosine kinase. Engineered: yes. Mutation: yes. Hepatocyte growth factor-like protein. Chain: c, d.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: mst1r, ptk8, ron. Expressed in: drosophila melanogaster. Expression_system_taxid: 7227. Gene: d3f15s2, dnf15s2, hgfl, msi1, mst1.

Resolution:

3.00Å R-factor: 0.237 R-free: 0.291

Authors:

O.Herzberg,K.L.Chao

Key ref:

K.L.Chao et al. (2014). Structural basis for the binding specificity of human Recepteur d'Origine Nantais (RON) receptor tyrosine kinase to macrophage-stimulating protein. J Biol Chem, 289, 29948-29960. PubMed id: 25193665 DOI: 10.1074/jbc.M114.594341

Date:

07-Jul-14 Release date: 17-Sep-14

Protein chains

Q04912  (RON_HUMAN) -  Macrophage-stimulating protein receptor from Homo sapiens

Seq: 1400 a.a.

Struc: 629 a.a.*

Protein chains

P26927  (HGFL_HUMAN) -  Hepatocyte growth factor-like protein from Homo sapiens

Seq: 711 a.a.

Struc: 231 a.a.*

* PDB and UniProt seqs differ at 7 residue positions (black crosses)

Enzyme reactions

• Enzyme class: Chains B, A: 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: 10.1074/jbc.M114.594341

J Biol Chem 289:29948-29960 (2014)

PubMed id: 25193665

Structural basis for the binding specificity of human Recepteur d'Origine Nantais (RON) receptor tyrosine kinase to macrophage-stimulating protein.

K.L.Chao, N.V.Gorlatova, E.Eisenstein, O.Herzberg.

ABSTRACT

Recepteur d'origine nantais (RON) receptor tyrosine kinase and its ligand, serum macrophage-stimulating protein (MSP), play important roles in inflammation, cell growth, migration, and epithelial to mesenchymal transition during tumor development. The binding of mature MSPαβ (disulfide-linked α- and β-chains) to RON ectodomain modulates receptor dimerization, followed by autophosphorylation of tyrosines in the cytoplasmic receptor kinase domains. Receptor recognition is mediated by binding of MSP β-chain (MSPβ) to the RON Sema. Here we report the structure of RON Sema-PSI-IPT1 (SPI1) domains in complex with MSPβ at 3.0 Å resolution. The MSPβ serine protease-like β-barrel uses the degenerate serine protease active site to recognize blades 2, 3, and 4 of the β-propeller fold of RON Sema. Despite the sequence homology between RON and MET receptor tyrosine kinase and between MSP and hepatocyte growth factor, it is well established that there is no cross-reactivity between the two receptor-ligand systems. Comparison of the structure of RON SPI1 in complex with MSPβ and that of MET receptor tyrosine kinase Sema-PSI in complex with hepatocyte growth factor β-chain reveals the receptor-ligand selectivity determinants. Analytical ultracentrifugation studies of the SPI1-MSPβ interaction confirm the formation of a 1:1 complex. SPI1 and MSPαβ also associate primarily as a 1:1 complex with a binding affinity similar to that of SPI1-MSPβ. In addition, the SPI1-MSPαβ ultracentrifuge studies reveal a low abundance 2:2 complex with ∼10-fold lower binding affinity compared with the 1:1 species. These results support the hypothesis that the α-chain of MSPαβ mediates RON dimerization.