 |
PDBsum entry 1nyf
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Phosphotransferase
|
PDB id
|
|
|
|
1nyf
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Solution structure and peptide binding of the sh3 domain from human fyn.
|
|
|
Authors
|
|
C.J.Morton,
D.J.Pugh,
E.L.Brown,
J.D.Kahmann,
D.A.Renzoni,
I.D.Campbell.
|
|
|
Ref.
|
|
Structure, 1996,
4,
705-714.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
Note In the PDB file this reference is
annotated as "TO BE PUBLISHED".
The citation details given above were identified by an automated
search of PubMed on title and author
names, giving a
perfect match.
|
|
|
|
Abstract
|
|
|
BACKGROUND: The Src family of tyrosine kinases is involved in the propagation of
intracellular signals from many transmembrane receptors. Each member of the
family contains two domains that regulate interactions with other molecules, one
of which is the Src homology 3 (SH3) domain. Although structures have previously
been determined for SH3 domains, and ideas about peptide-binding modes have been
proposed, their physiological role is still unclear. RESULTS: We have determined
the solution structure of the SH3 domain from the Src family tyrosine kinase Fyn
in two forms: unbound and complexed with a peptide corresponding to a putative
ligand sequence from phosphatidylinositol 3' kinase. Fyn SH3 shows the typical
SH3 topology of two perpendicular three-stranded beta sheets and a single turn
of 3(10) helix. The interaction of SH3 with three potential ligand peptides was
investigated, demonstrating that they all bind to the same site on the molecule.
A previous model for ligand binding to SH3 domains predicts binding in one of
two orientations (class I or II), each characterized by a consensus sequence.
The ligand with the closest match to the class I consensus sequence bound with
highest affinity and in the predicted orientation. CONCLUSIONS: The Fyn SH3
domain has a well-defined structure in solution. The relative binding affinities
of the three ligand peptides and their orientation within the Fyn SH3 complex
were consistent with recently proposed models for the binding of 'consensus'
polyproline sequences. Although the affinities of consensus and non-consensus
peptides are different, the degree of difference is not very large, suggesting
that SH3 domains bind to polyproline peptides in a promiscuous manner.
|
|
|
|
|
|
|
|
Figure 3.
Figure 3. Diagrammatic representation of the Fyn SH3 structure,
showing the position of the two β sheets and the single turn
of 3[10] helix. Strands are coloured green in β sheet I and
yellow in β sheet II, with the 3[10] helix coloured blue. The
N and C termini are indicated. This figure was prepared with
the programs MOLSCRIPT [45] and Raster3D [46 and 47]. Figure
3. Diagrammatic representation of the Fyn SH3 structure, showing
the position of the two β sheets and the single turn of 3[10]
helix. Strands are coloured green in β sheet I and yellow in β
sheet II, with the 3[10] helix coloured blue. The N and C
termini are indicated. This figure was prepared with the
programs MOLSCRIPT [[3]45] and Raster3D [[4]46 and [5]47].
|
|
Figure 4.
Figure 4. The structure of the Fyn SH3–peptide 2 complex. The
protein is shown as a backbone worm, with residues displaying
NOE crosspeaks with the peptide shown as sticks. These are
Tyr91 (red), Tyr137 (cyan), Asn136 (yellow) and Trp119 (green).
The peptide is displayed as a ball and stick structure,
coloured by atom type, with the N terminus on the right of the
picture. Figure 4. The structure of the Fyn SH3–peptide 2
complex. The protein is shown as a backbone worm, with residues
displaying NOE crosspeaks with the peptide shown as sticks.
These are Tyr91 (red), Tyr137 (cyan), Asn136 (yellow) and Trp119
(green). The peptide is displayed as a ball and stick structure,
coloured by atom type, with the N terminus on the right of the
picture.
|
|
|
|
|
|
The above figures are
reprinted
by permission from Cell Press:
Structure
(1996,
4,
705-714)
copyright 1996.
|
|
|
Secondary reference #1
|
|
|
Title
|
|
Crystal structure of the sh3 domain in human fyn; comparison of the three-Dimensional structures of sh3 domains in tyrosine kinases and spectrin.
|
|
|
Authors
|
|
M.E.Noble,
A.Musacchio,
M.Saraste,
S.A.Courtneidge,
R.K.Wierenga.
|
|
|
Ref.
|
|
Embo J, 1993,
12,
2617-2624.
|
|
|
PubMed id
|
|
|
|
|
|
|
|
|
|
|
|
|
