Database Accession: DI1020003
Name: SH2 domain from the tyrosine kinase Fyn in complex with middle T antigen peptide
PDB ID: 1aou
Experimental method: NMR
Source organism: Hamster polyomavirus / Homo sapiens
Proof of disorder:
Primary publication of the structure:
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.
(1997) Structure 5: 1313-23
PMID: 9351806
Abstract:
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.
Annotations from the GeneOntology database. Only terms that fit at least two of the interacting proteins are shown.Molecular function: not assigned
Biological process:
Cellular component:
membrane A lipid bilayer along with all the proteins and protein complexes embedded in it an attached to it.
Structural annotations of the participating protein chains.Entry contents: 2 distinct polypeptide molecules
Chains: P, F
Notes: No modifications of the original PDB file.
Name: Middle T antigen
Source organism: Hamster polyomavirus
Length: 11 residues
Sequence:Sequence according to PDB SEQRESEPQYEEIPIYL
The sequence contains the following modified/non-standard residues:
• phosphotyrosine (Y) at position 324 (PDB position: 204)
UniProtKB AC: P03079 (positions: 321-331) Coverage: 2.7%
UniRef90 AC: UniRef90_P03079 (positions: 321-331)
Name: Tyrosine-protein kinase Fyn
Source organism: Homo sapiens
Length: 106 residues
Sequence:Sequence according to PDB SEQRESSIQAEEWYFGKLGRKDAERQLLSFGNPRGTFLIRESETTKGAYSLSIRDWDDMKGDHVKHYKIRKLDNGGYYITTRAQFETLQQLVQHYSERAAGLSSRLVVPSHK
UniProtKB AC: P06241 (positions: 143-248) Coverage: 19.7%
UniRef90 AC: UniRef90_P06241 (positions: 143-248)
Evidence demonstrating that the participating proteins are unstructured prior to the interaction and their folding is coupled to binding. Chain P:
The protein region involved in the interaction contains a known functional linear motif (LIG_SH2_SRC).
Chain 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.
Structures from the PDB that contain the same number of proteins, and the proteins from the two structures show a sufficient degree of pairwise similarity, i.e. they belong to the same UniRef90 cluster (the full proteins exhibit at least 90% sequence identity) and convey roughly the same region to their respective interactions (the two regions from the two proteins share a minimum of 70% overlap). The structure can be rotated by left click and hold anywhere on the structure. Representation options can be edited by right clicking on the structure window.
