DI1020003
SH2 domain from the tyrosine kinase Fyn in complex with middle T antigen peptide
1aou
NMR
Hamster polyomavirus / Homo sapiens
Inferred from motif
9351806
Mulhern TD, Shaw GL, Morton CJ, Day AJ, Campbell ID
The SH2 domain from the tyrosine kinase Fyn in complex with a phosphotyrosyl peptide reveals insights into domain stability and binding specificity.
Structure
1997
10
5
1313-23
CONCLUSIONS: Comparison of the Fyn SH2 domain structure with other structures of SH2 domains highlights several interesting features. Conservation of helix capping interactions among various SH2 domains is suggestive of a role in protein stabilisation. The presence of a type-I' turn in the BG loop, which is dependent on the presence of a glycine residue at position BG3, is indicative of a binding pocket, characteristic of the Src family, SykC and Abl, rather than a binding groove found in PLC-gamma 1C, p85 alpha N and Shc, for example. RESULTS: The structure of the Fyn SH2 domain in complex with a phosphotyrosyl peptide (EPQpYEEIPIYL) was determined by high resolution NMR spectroscopy. The overall structure of the complex is analogous to that of other SH2-peptide complexes. Noteworthy aspects of the structure are: the BG loop, which contacts the bound peptide, contains a type-I' turn; a capping-box-like interaction is present at the N-terminal end of helix alpha A; cis-trans isomerization of the Val beta G1-Pro beta G2 peptide bond causes conformational heterogeneity of residues near the N and C termini of the domain. BACKGROUND: SH2 domains are found in a variety of signal transduction proteins; they bind phosphotyrosine-containing sequences, allowing them to both recognize target molecules and regulate intramolecular kinase activity. Fyn is a member of the Src family of tyrosine kinases that are involved in signal transduction by association with a number of membrane receptors. The kinase activity of these signalling proteins is modulated by switching the binding mode of their SH2 and SH3 domains from intramolecular to intermolecular. The molecular basis of the signalling roles observed for different Src family members is still not well understood; although structures have been determined for the SH2 domains of other Src family molecules, this is the first structure of the Fyn SH2 domain.
GO:0016032
viral process
GO:0016020
membrane
No modifications of the original PDB file.
2
SH2
P
Middle T antigen
Disordered
Hamster polyomavirus
EPQYEEIPIYL
204
324
Y
phosphotyrosine
11
P03079
321
331
2.7%
UniRef90_P03079
321
331
F
Tyrosine-protein kinase Fyn
Ordered
Homo sapiens
SIQAEEWYFGKLGRKDAERQLLSFGNPRGTFLIRESETTKGAYSLSIRDWDDMKGDHVKHYKIRKLDNGGYYITTRAQFETLQQLVQHYSERAAGLSSRLVVPSHK
106
P06241
143
248
19.7%
UniRef90_P06241
143
248
secondary structure
beta
152
152
secondary structure
helix
156
164
secondary structure
beta
172
172
secondary structure
beta
176
176
secondary structure
beta
178
178
secondary structure
beta
184
190
secondary structure
beta
193
193
secondary structure
beta
197
197
secondary structure
beta
200
207
secondary structure
beta
213
216
secondary structure
beta
219
221
secondary structure
helix
224
233
pfam
PF00017.21
SH2
149
231
P
The protein region involved in the interaction contains a known functional linear motif (LIG_SH2_SRC).
F
The SH2 domain involved in the interaction is known to adopt a stable structure in isolation (see Pfam domain PF00017). A solved monomeric structure of the domain from a homologous protein is represented by PDB ID 1ab2.
1aot
4u1p