PDBsum entry 2fci

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protein Protein-protein interface(s) links
Hydrolase PDB id
Protein chains
14 a.a.
105 a.a. *
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: Structural basis for the requirement of two phosphotyrosines signaling mediated by syk tyrosine kinase
Structure: Doubly phosphorylated peptide derived from syk ki comprising residues 338-350. Chain: b. Fragment: phosphopeptide from syk kinase. Engineered: yes. C-termainl sh2 domain from phospholipasE C-gamma- comprising residues 663-759. Chain: a. Fragment: c-terminal sh2 domain.
Source: Synthetic: yes. Other_details: peptide synthesis. Bos taurus. Cattle. Organism_taxid: 9913. Gene: plcg1. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Expression_system_variant: bl21(de3).
NMR struc: 16 models
Authors: T.D.Groesch,F.Zhou,S.Mattila,R.L.Geahlen,C.B.Post
Key ref:
T.D.Groesch et al. (2006). Structural basis for the requirement of two phosphotyrosine residues in signaling mediated by syk tyrosine kinase. J Mol Biol, 356, 1222-1236. PubMed id: 16410013 DOI: 10.1016/j.jmb.2005.11.095
12-Dec-05     Release date:   31-Jan-06    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q32PK0  (Q32PK0_BOVIN) -  Tyrosine-protein kinase
605 a.a.
13 a.a.*
Protein chain
Pfam   ArchSchema ?
P08487  (PLCG1_BOVIN) -  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1
1291 a.a.
105 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 9 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class 1: Chain A: E.C.  - Phosphoinositide phospholipase C.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

myo-Inositol Phosphate Metabolism
      Reaction: 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate + H2O = 1D-myo-inositol 1,4,5-trisphosphate + diacylglycerol
1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate
+ H(2)O
= 1D-myo-inositol 1,4,5-trisphosphate
+ diacylglycerol
   Enzyme class 2: Chain B: E.C.  - Non-specific protein-tyrosine kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate
+ [protein]-L-tyrosine
+ [protein]-L-tyrosine phosphate
Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.
Molecule diagrams generated from .mol files obtained from the KEGG ftp site


DOI no: 10.1016/j.jmb.2005.11.095 J Mol Biol 356:1222-1236 (2006)
PubMed id: 16410013  
Structural basis for the requirement of two phosphotyrosine residues in signaling mediated by syk tyrosine kinase.
T.D.Groesch, F.Zhou, S.Mattila, R.L.Geahlen, C.B.Post.
The protein-tyrosine kinase Syk couples immune recognition receptors to multiple signal transduction pathways, including the mobilization of calcium and the activation of NFAT. The ability of Syk to regulate signaling is influenced by its phosphorylation on tyrosine residues within the linker B region. The phosphorylation of both Y342 and Y346 is necessary for optimal signaling from the B cell receptor for antigen. The SH2 domains of multiple signaling proteins share the ability to bind this doubly phosphorylated site. The NMR structure of the C-terminal SH2 domain of PLCgamma (PLCC) bound to a doubly phosphorylated Syk peptide reveals a novel mode of phosphotyrosine recognition. PLCC undergoes extensive conformational changes upon binding to form a second phosphotyrosine-binding pocket in which pY346 is largely desolvated and stabilized through electrostatic interactions. The formation of the second binding pocket is distinct from other modes of phosphotyrosine recognition in SH2-protein association. The dependence of signaling on simultaneous phosphorylation of these two tyrosine residues offers a new mechanism to fine-tune the cellular response to external stimulation.
  Selected figure(s)  
Figure 4.
Figure 4. Structure of the PLCC-pYpY complex. (a) Overlay of the final 15 structures of the PLCC-pYpY complex (residues 10-97). The structures were aligned by the central b-sheet of PLCC. The protein is shown in grey and the peptide is shown in cyan. (b) The energy-minimized average structure of the PLCC-pYpY complex. The protein is shown in grey, and the peptide is shown in cyan with the pTyr residues highlighted in red.
Figure 7.
Figure 7. The binding of pYpY induces changes of conformation in PLCC. (a) Stereoview of the comparison of PLCC bound to either the singly phosphorylated pYpY (grey) or pY1021 (yellow) and aligned on the basis of the central b-sheet of the protein. Large changes exist for aA, aB, bD, the BG loop, and the secondary b-sheet. (b) Surface representation of PLCC bound to pYpY. The electrostatic potential of the proteins calculated with the program GRASP is mapped on the surface of the protein. (c) Surface representation of PLCC bound to pY1021. The two structures in (b) and (c) were aligned, and any differences between the two surfaces arise from differences in the protein conformation not protein orientation.
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2006, 356, 1222-1236) copyright 2006.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20870410 T.D.Bunney, and M.Katan (2011).
PLC regulation: emerging pictures for molecular mechanisms.
  Trends Biochem Sci, 36, 88-96.  
20467426 A.Mócsai, J.Ruland, and V.L.Tybulewicz (2010).
The SYK tyrosine kinase: a crucial player in diverse biological functions.
  Nat Rev Immunol, 10, 387-402.  
19409513 E.Arias-Palomo, M.A.Recuero-Checa, X.R.Bustelo, and O.Llorca (2009).
Conformational rearrangements upon Syk auto-phosphorylation.
  Biochim Biophys Acta, 1794, 1211-1217.  
19665973 J.H.Bae, E.D.Lew, S.Yuzawa, F.Tomé, I.Lax, and J.Schlessinger (2009).
The selectivity of receptor tyrosine kinase signaling is controlled by a secondary SH2 domain binding site.
  Cell, 138, 514-524.
PDB codes: 3gqi 3gql
19955438 L.Min, R.E.Joseph, D.B.Fulton, and A.H.Andreotti (2009).
Itk tyrosine kinase substrate docking is mediated by a nonclassical SH2 domain surface of PLCgamma1.
  Proc Natl Acad Sci U S A, 106, 21143-21148.  
19123268 P.De, Q.Peng, D.O.Traktuev, D.O.Traktuevc, W.Li, M.C.Yoder, K.L.March, and D.L.Durden (2009).
Expression of RAC2 in endothelial cells is required for the postnatal neovascular response.
  Exp Cell Res, 315, 248-263.  
19306898 R.L.Geahlen (2009).
Syk and pTyr'd: Signaling through the B cell antigen receptor.
  Biochim Biophys Acta, 1793, 1115-1127.  
19001411 S.Hanke, and M.Mann (2009).
The phosphotyrosine interactome of the insulin receptor family and its substrates IRS-1 and IRS-2.
  Mol Cell Proteomics, 8, 519-534.  
18767163 W.Gan, and B.Roux (2009).
Binding specificity of SH2 domains: insight from free energy simulations.
  Proteins, 74, 996.  
19435818 X.Zhang, U.Shrikhande, B.M.Alicie, Q.Zhou, and R.L.Geahlen (2009).
Role of the protein tyrosine kinase Syk in regulating cell-cell adhesion and motility in breast cancer cells.
  Mol Cancer Res, 7, 634-644.  
19909371 Y.Kulathu, G.Grothe, and M.Reth (2009).
Autoinhibition and adapter function of Syk.
  Immunol Rev, 232, 286-299.  
18369315 Y.Kulathu, E.Hobeika, G.Turchinovich, and M.Reth (2008).
The kinase Syk as an adaptor controlling sustained calcium signalling and B-cell development.
  EMBO J, 27, 1333-1344.  
18689684 Y.Zhang, H.Oh, R.A.Burton, J.W.Burgner, R.L.Geahlen, and C.B.Post (2008).
Tyr130 phosphorylation triggers Syk release from antigen receptor by long-distance conformational uncoupling.
  Proc Natl Acad Sci U S A, 105, 11760-11765.  
18021750 E.Arias-Palomo, M.A.Recuero-Checa, X.R.Bustelo, and O.Llorca (2007).
3D structure of Syk kinase determined by single-particle electron microscopy.
  Biochim Biophys Acta, 1774, 1493-1499.  
17987119 J.Schymeinsky, C.Then, A.Sindrilaru, R.Gerstl, Z.Jakus, V.L.Tybulewicz, K.Scharffetter-Kochanek, and B.Walzog (2007).
Syk-Mediated Translocation of PI3Kdelta to the Leading Edge Controls Lamellipodium Formation and Migration of Leukocytes.
  PLoS ONE, 2, e1132.  
18074396 R.L.Rich, and D.G.Myszka (2007).
Survey of the year 2006 commercial optical biosensor literature.
  J Mol Recognit, 20, 300-366.  
16793553 B.A.Liu, K.Jablonowski, M.Raina, M.Arcé, T.Pawson, and P.D.Nash (2006).
The human and mouse complement of SH2 domain proteins-establishing the boundaries of phosphotyrosine signaling.
  Mol Cell, 22, 851-868.  
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 codes are shown on the right.