 |
PDBsum entry 4qt8
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Hydrolase/signaling protein
|
PDB id
|
|
|
|
4qt8
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Structural basis for the binding specificity of human recepteur d'Origine nantais (ron) receptor tyrosine kinase to macrophage-Stimulating protein.
|
|
|
Authors
|
|
K.L.Chao,
N.V.Gorlatova,
E.Eisenstein,
O.Herzberg.
|
|
|
Ref.
|
|
J Biol Chem, 2014,
289,
29948-29960.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
