 |
PDBsum entry 1ju5
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Protein binding/transferase
|
PDB id
|
|
|
|
1ju5
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Structure of a regulatory complex involving the abl sh3 domain, The crk sh2 domain, And a crk-Derived phosphopeptide.
|
|
|
Authors
|
|
L.W.Donaldson,
G.Gish,
T.Pawson,
L.E.Kay,
J.D.Forman-Kay.
|
|
|
Ref.
|
|
Proc Natl Acad Sci U S A, 2002,
99,
14053-14058.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
On phosphorylation of Y221 by Abelson (Abl) kinase, the Crk-II adapter protein
undergoes an intramolecular reorganization initiated by the binding of its own
Src homology 2 (SH2) domain to the pY221 site. Conformational changes induced by
phosphotyrosine recognition promote the binding of the Src homology 3 (SH3)
domain of the Abl tyrosine kinase to a proline-rich loop located between the
betaD and betaE strands of the SH2 domain (DE loop). We have determined the NMR
solution structure of the ternary complex of the Abl SH3 domain with the Crk SH2
domain bound to a Crk pY221 phosphopeptide. The SH2 domain bridges two ligands
that bind at distinct sites. The interaction between the Abl SH3 domain and the
Crk SH2 domain is localized to a canonical eight-residue site within the DE
loop. From (15)N relaxation experiments, the DE loop of the SH2 domain in the
complex displays a significant degree of conformational freedom. The structural
and dynamic data therefore indicate that these SH2 and SH3 domains do not assume
a unique orientation with respect to one another; rather, they appear to be only
tethered via the DE loop. Thus, SH2 domain-SH3 domain interactions do not
require additional tertiary contacts or restriction of domain orientation when a
recognition motif is presented in a mobile loop. This complex between the Abl
SH3 domain, Crk SH2 domain, and Crk phosphopeptide is an example of the
extremely modular nature of regulatory proteins that provides a rich repertoire
of mechanisms for control of biological function.
|
|
|
|
|
|
|
|
Figure 1.
Fig 1. The complex described in this study includes the Abl
SH3 domain (green), the Crk SH2 domain (yellow), and a 13-aa
phosphopeptide corresponding to the Crk SH2 internal binding
site (blue).
|
|
Figure 4.
Fig 4. (Upper) Detail of the Crk SH2 domain bound to the
Crk phosphopeptide (residues 221-224) in the ternary complex.
Residues observed to make contacts are highlighted. (Lower)
Sequence comparison of Crk-II with homologues v-Crk and CrkL.
The sequence of murine Crk-II corresponds to the protein
fragment described in this study. Only Crk-II contains a binding
site for the Abl SH3 domain (shaded box).
|
|
|
|
|
|
|
|
|
|
