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PDBsum entry 1aot

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protein Protein-protein interface(s) links
Complex (proto-oncogene/early protein) PDB id
1aot
Jmol PyMol
Contents
Protein chains
106 a.a. *
11 a.a. *
* Residue conservation analysis
PDB id:
1aot
Name: Complex (proto-oncogene/early protein)
Title: Nmr structure of the fyn sh2 domain complexed with a phosphotyrosyl peptide, minimized average structure
Structure: Fyn protein-tyrosine kinase. Chain: f. Fragment: sh2 domain. Synonym: src homology 2 domain. Engineered: yes. Mutation: yes. Phosphotyrosyl peptide. Chain: p
Source: Homo sapiens. Human. Organism_taxid: 9606. Cell_line: bl21. Gene: lyss. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Hamster polyomavirus. Organism_taxid: 10626
NMR struc: 1 models
Authors: T.D.Mulhern,G.L.Shaw,C.J.Morton,A.J.Day,I.D.Campbell
Key ref:
T.D.Mulhern et al. (1997). The SH2 domain from the tyrosine kinase Fyn in complex with a phosphotyrosyl peptide reveals insights into domain stability and binding specificity. Structure, 5, 1313-1323. PubMed id: 9351806 DOI: 10.1016/S0969-2126(97)00283-9
Date:
10-Jul-97     Release date:   14-Jan-98    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P06241  (FYN_HUMAN) -  Tyrosine-protein kinase Fyn
Seq:
Struc:
 
Seq:
Struc:
537 a.a.
106 a.a.*
Protein chain
Pfam   ArchSchema ?
P03079  (MT_POVHA) -  Middle T antigen
Seq:
Struc:
401 a.a.
11 a.a.
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 3 residue positions (black crosses)

 

 
DOI no: 10.1016/S0969-2126(97)00283-9 Structure 5:1313-1323 (1997)
PubMed id: 9351806  
 
 
The SH2 domain from the tyrosine kinase Fyn in complex with a phosphotyrosyl peptide reveals insights into domain stability and binding specificity.
T.D.Mulhern, G.L.Shaw, C.J.Morton, A.J.Day, I.D.Campbell.
 
  ABSTRACT  
 
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. 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. 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.
 
  Selected figure(s)  
 
Figure 2.
Figure 2. Stereoview of the C^a trace of the energy minimised average coordinates. The C^a atom of every 10th residue is labelled and the non-hydrogen atoms of the peptide residues which interact with the protein (pY, +1E, +2E and +3I) are shown.
 
  The above figure is reprinted by permission from Cell Press: Structure (1997, 5, 1313-1323) copyright 1997.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20661443 M.Sylvester, S.Kliche, S.Lange, S.Geithner, C.Klemm, A.Schlosser, A.Grossmann, U.Stelzl, B.Schraven, E.Krause, and C.Freund (2010).
Adhesion and degranulation promoting adapter protein (ADAP) is a central hub for phosphotyrosine-mediated interactions in T cells.
  PLoS One, 5, e11708.  
19805512 C.Brignatz, M.P.Paronetto, S.Opi, M.Cappellari, S.Audebert, V.Feuillet, G.Bismuth, S.Roche, S.T.Arold, C.Sette, and Y.Collette (2009).
Alternative splicing modulates autoinhibition and SH3 accessibility in the Src kinase Fyn.
  Mol Cell Biol, 29, 6438-6448.  
18579586 M.Rovedo, and R.Longnecker (2008).
Epstein-Barr virus latent membrane protein 2A preferentially signals through the Src family kinase Lyn.
  J Virol, 82, 8520-8528.  
18842137 T.Lenaerts, J.Ferkinghoff-Borg, F.Stricher, L.Serrano, J.W.Schymkowitz, and F.Rousseau (2008).
Quantifying information transfer by protein domains: analysis of the Fyn SH2 domain structure.
  BMC Struct Biol, 8, 43.  
11684687 S.E.Pursglove, T.D.Mulhern, J.P.Mackay, M.G.Hinds, and G.W.Booker (2002).
The solution structure and intramolecular associations of the Tec kinase SRC homology 3 domain.
  J Biol Chem, 277, 755-762.
PDB code: 1gl5
12121645 T.S.Ulmer, J.M.Werner, and I.D.Campbell (2002).
SH3-SH2 domain orientation in Src kinases: NMR studies of Fyn.
  Structure, 10, 901-911.  
  10850802 S.P.Edgcomb, B.M.Baker, and K.P.Murphy (2000).
The energetics of phosphate binding to a protein complex.
  Protein Sci, 9, 927-933.  
  10548041 E.W.Chung, D.A.Henriques, D.Renzoni, C.J.Morton, T.D.Mulhern, M.C.Pitkeathly, J.E.Ladbury, and C.V.Robinson (1999).
Probing the nature of interactions in SH2 binding interfaces--evidence from electrospray ionization mass spectrometry.
  Protein Sci, 8, 1962-1970.  
10051576 R.Briesewitz, G.T.Ray, T.J.Wandless, and G.R.Crabtree (1999).
Affinity modulation of small-molecule ligands by borrowing endogenous protein surfaces.
  Proc Natl Acad Sci U S A, 96, 1953-1958.  
9799501 J.M.Bradshaw, and G.Waksman (1998).
Calorimetric investigation of proton linkage by monitoring both the enthalpy and association constant of binding: application to the interaction of the Src SH2 domain with a high-affinity tyrosyl phosphopeptide.
  Biochemistry, 37, 15400-15407.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.

 

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