 |
PDBsum entry 2k6d
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Sh3 domain/ubiquitin
|
PDB id
|
|
|
|
2k6d
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Interactions between the three cin85 sh3 domains and ubiquitin: implications for cin85 ubiquitination.
|
|
|
Authors
|
|
I.Bezsonova,
M.C.Bruce,
S.Wiesner,
H.Lin,
D.Rotin,
J.D.Forman-Kay.
|
|
|
Ref.
|
|
Biochemistry, 2008,
47,
8937-8949.
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
CIN85 is an adaptor protein linking the ubiquitin ligase Cbl and
clathrin-binding proteins in clathrin-mediated receptor endocytosis. The SH3
domains of CIN85 bind to a proline-rich region of Cbl. Here we show that all
three SH3 domains of CIN85 bind to ubiquitin. We also present a data-based
structural model of the CIN85 SH3-C domain in complex with ubiquitin. In this
complex, ubiquitin binds to the canonical interaction surface of the SH3 domain
for proline-rich ligands and mimics the PPII helix, and we provide evidence that
ubiquitin competes with these ligands for binding. We demonstrate that
disruption of ubiquitin binding results in constitutive ubiquitination of CIN85
and an increased level of ubiquitination of EGFR in the absence of EGF
stimulation. These results suggest that competition between Cbl and ubiquitin
binding to CIN85 regulates Cbl function and EGFR endocytosis.
|
|
|
|
|
|
|
