 |
PDBsum entry 4hxj
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Blood clotting, signaling protein
|
PDB id
|
|
|
|
4hxj
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Structural framework of c-Src activation by integrin β3.
|
|
|
Authors
|
|
R.Xiao,
X.D.Xi,
Z.Chen,
S.J.Chen,
G.Meng.
|
|
|
Ref.
|
|
Blood, 2013,
121,
700-706.
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
The integrin β3-mediated c-Src priming and activation, via the SH3 domain, is
consistently associated with diseases, such as the formation of thrombosis and
the migration of tumor cells. Conventionally, activation of c-Src is often
induced by the binding of proline-rich sequences to its SH3 domain. Instead,
integrin β3 uses R(760)GT(762) for priming and activation. Because of the lack
of structural information, it is not clear where RGT will bind to SH3, and under
what mechanism this interaction can prime/activate c-Src. In this study, we
present a 2.0-Å x-ray crystal structure in which SH3 is complexed with the RGT
peptide. The binding site lies in the "N"-Src loop of the SH3 domain.
Structure-based site-directed mutagenesis showed that perturbation on the
"N"-Src loop disrupts the interaction between the SH3 domain and the
RGT peptide. Furthermore, the simulated c-Src:β3 complex based on the crystal
structure of SH3:RGT suggests that the binding of the RGT peptide might disrupt
the intramolecular interaction between the SH3 and linker domains, leading to
the disengagement of Trp260:"C"-helix and further activation of c-Src.
|
|
|
|
|
|
|
