spacer
spacer
Go to PDB code: 
protein Protein-protein interface(s) links
Complex (signal transduction/peptide) PDB id
1irs
Jmol
Contents
Protein chains
112 a.a. *
11 a.a. *
* Residue conservation analysis
PDB id:
1irs
Name: Complex (signal transduction/peptide)
Title: Irs-1 ptb domain complexed with a il-4 receptor phosphopeptide, nmr, minimized average structure
Structure: Irs-1. Chain: a. Fragment: ptb domain. Synonym: insulin receptor substrate 1. Engineered: yes. Il-4 receptor phosphopeptide. Chain: b. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Strain: bl21 (de2) plyss. Cell_line: bl21. Organ: skeletal. Gene: ptb domain of irs-1. Expressed in: escherichia coli. Expression_system_taxid: 562.
NMR struc: 1 models
Authors: M.-M.Zhou,B.Huang,E.T.Olejniczak,R.P.Meadows,S.B.Shuker, M.Miyazaki,T.Trub,S.E.Shoelson,S.W.Feisk
Key ref: M.M.Zhou et al. (1996). Structural basis for IL-4 receptor phosphopeptide recognition by the IRS-1 PTB domain. Nat Struct Biol, 3, 388-393. PubMed id: 8599766 DOI: 10.1038/nsb0496-388
Date:
22-Mar-96     Release date:   15-May-97    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P35568  (IRS1_HUMAN) -  Insulin receptor substrate 1
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		1242 a.a.
112 a.a.*
Protein chain
Pfam   ArchSchema ?
P24394  (IL4RA_HUMAN) -  Interleukin-4 receptor subunit alpha
Seq:
Struc: 		 
Seq:
Struc: 		825 a.a.
11 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biochemical function     insulin receptor binding     1 term  

 

 
DOI no: 10.1038/nsb0496-388 Nat Struct Biol 3:388-393 (1996)
PubMed id: 8599766  
 
 
Structural basis for IL-4 receptor phosphopeptide recognition by the IRS-1 PTB domain.
M.M.Zhou, B.Huang, E.T.Olejniczak, R.P.Meadows, S.B.Shuker, M.Miyazaki, T.Trüb, S.E.Shoelson, S.W.Fesik.
 
  ABSTRACT  
 
We present the NMR structure of the PTB domain of insulin receptor substrate-1 (IRS-1) complexed to a tyrosine-phosphorylated peptide derived from the IL-4 receptor. Despite the lack of sequence homology and different binding specificity, the overall fold of the protein is similar to that of the Shc PTB domain and closely resembles that of PH domains. However, the PTB domain of IRS-1 is smaller than that of Shc (110 versus 170 residues) and binds to phosphopeptides in a distinct manner. We explain the phosphopeptide binding specificity based on the structure of the complex and results of site-directed mutagenesis experiments.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20454865 S.Koshiba, H.Li, Y.Motoda, T.Tomizawa, T.Kasai, N.Tochio, T.Yabuki, T.Harada, S.Watanabe, A.Tanaka, M.Shirouzu, T.Kigawa, T.Yamamoto, and S.Yokoyama (2010).
Structural basis for the recognition of nucleophosmin-anaplastic lymphoma kinase oncoprotein by the phosphotyrosine binding domain of Suc1-associated neurotrophic factor-induced tyrosine-phosphorylated target-2.
  J Struct Funct Genomics, 11, 125-141.
PDB codes: 2kup 2kuq 2ys5 2yt2
18819102 S.O.Lee, J.Y.Chun, N.Nadiminty, W.Lou, S.Feng, and A.C.Gao (2009).
Interleukin-4 activates androgen receptor through CBP/p300.
  Prostate, 69, 126-132.  
18721752 A.Kaushansky, A.Gordus, B.A.Budnik, W.S.Lane, J.Rush, and G.MacBeath (2008).
System-wide investigation of ErbB4 reveals 19 sites of Tyr phosphorylation that are unusually selective in their recruitment properties.
  Chem Biol, 15, 808-817.  
18493663 A.Kaushansky, A.Gordus, B.Chang, J.Rush, and G.MacBeath (2008).
A quantitative study of the recruitment potential of all intracellular tyrosine residues on EGFR, FGFR1 and IGF1R.
  Mol Biosyst, 4, 643-653.  
18650440 H.Li, S.Koshiba, F.Hayashi, N.Tochio, T.Tomizawa, T.Kasai, T.Yabuki, Y.Motoda, T.Harada, S.Watanabe, M.Inoue, Y.Hayashizaki, A.Tanaka, T.Kigawa, and S.Yokoyama (2008).
Structure of the C-terminal phosphotyrosine interaction domain of Fe65L1 complexed with the cytoplasmic tail of amyloid precursor protein reveals a novel peptide binding mode.
  J Biol Chem, 283, 27165-27178.
PDB codes: 1wgu 2roz 2ysz 2yt0 2yt1
18550529 J.Radzimanowski, S.Ravaud, S.Schlesinger, J.Koch, K.Beyreuther, I.Sinning, and K.Wild (2008).
Crystal structure of the human Fe65-PTB1 domain.
  J Biol Chem, 283, 23113-23120.
PDB codes: 3d8d 3d8e 3d8f
18008330 S.O.Lee, E.Pinder, J.Y.Chun, W.Lou, M.Sun, and A.C.Gao (2008).
Interleukin-4 stimulates androgen-independent growth in LNCaP human prostate cancer cells.
  Prostate, 68, 85-91.  
17473008 C.J.McCleverty, D.C.Lin, and R.C.Liddington (2007).
Structure of the PTB domain of tensin1 and a model for its recruitment to fibrillar adhesions.
  Protein Sci, 16, 1223-1229.
PDB code: 1wvh
16828554 H.Remaut, and G.Waksman (2006).
Protein-protein interaction through beta-strand addition.
  Trends Biochem Sci, 31, 436-444.  
16496021 P.Aloy, and R.B.Russell (2006).
Structural systems biology: modelling protein interactions.
  Nat Rev Mol Cell Biol, 7, 188-197.  
15678501 S.O.Lee, W.Lou, N.Nadiminty, X.Lin, and A.C.Gao (2005).
Requirement for NF-(kappa)B in interleukin-4-induced androgen receptor activation in prostate cancer cells.
  Prostate, 64, 160-167.  
14607833 N.Shi, S.Ye, M.Bartlam, M.Yang, J.Wu, Y.Liu, F.Sun, X.Han, X.Peng, B.Qiang, J.Yuan, and Z.Rao (2004).
Structural basis for the specific recognition of RET by the Dok1 phosphotyrosine binding domain.
  J Biol Chem, 279, 4962-4969.
PDB codes: 1p5t 1uef
  12906822 A.Farooq, L.Zeng, K.S.Yan, K.S.Ravichandran, and M.M.Zhou (2003).
Coupling of folding and binding in the PTB domain of the signaling protein Shc.
  Structure, 11, 905-913.
PDB codes: 1n3h 1oy2
12435749 A.Q.Sun, R.Salkar, Sachchidanand, S.Xu, L.Zeng, M.M.Zhou, and F.J.Suchy (2003).
A 14-amino acid sequence with a beta-turn structure is required for apical membrane sorting of the rat ileal bile acid transporter.
  J Biol Chem, 278, 4000-4009.  
  12737812 K.S.Yan, and M.M.Zhou (2003).
Examining both sides of a Janus PTB domain.
  Structure, 11, 482-484.  
12766170 L.S.Lock, M.M.Frigault, C.Saucier, and M.Park (2003).
Grb2-independent recruitment of Gab1 requires the C-terminal lobe and structural integrity of the Met receptor kinase domain.
  J Biol Chem, 278, 30083-30090.  
12826668 M.Yun, L.Keshvara, C.G.Park, Y.M.Zhang, J.B.Dickerson, J.Zheng, C.O.Rock, T.Curran, and H.W.Park (2003).
Crystal structures of the Dab homology domains of mouse disabled 1 and 2.
  J Biol Chem, 278, 36572-36581.
PDB codes: 1m7e 1oqn 1p3r
12665569 N.Jones, S.H.Chen, C.Sturk, Z.Master, J.Tran, R.S.Kerbel, and D.J.Dumont (2003).
A unique autophosphorylation site on Tie2/Tek mediates Dok-R phosphotyrosine binding domain binding and function.
  Mol Cell Biol, 23, 2658-2668.  
11932255 D.A.Calderwood, B.Yan, J.M.de Pereda, B.G.Alvarez, Y.Fujioka, R.C.Liddington, and M.H.Ginsberg (2002).
The phosphotyrosine binding-like domain of talin activates integrins.
  J Biol Chem, 277, 21749-21758.  
11788580 H.Xiao, T.Yin, X.Y.Wang, T.Uchida, J.Chung, M.F.White, and Y.C.Yang (2002).
Specificity of interleukin-2 receptor gamma chain superfamily cytokines is mediated by insulin receptor substrate-dependent pathway.
  J Biol Chem, 277, 8091-8098.  
11877385 K.S.Yan, M.Kuti, S.Yan, S.Mujtaba, A.Farooq, M.P.Goldfarb, and M.M.Zhou (2002).
FRS2 PTB domain conformation regulates interactions with divergent neurotrophic receptors.
  J Biol Chem, 277, 17088-17094.  
12058075 L.S.Lock, C.R.Maroun, M.A.Naujokas, and M.Park (2002).
Distinct recruitment and function of Gab1 and Gab2 in Met receptor-mediated epithelial morphogenesis.
  Mol Biol Cell, 13, 2132-2146.  
11090629 C.Dhalluin, K.S.Yan, O.Plotnikova, K.W.Lee, L.Zeng, M.Kuti, S.Mujtaba, M.P.Goldfarb, and M.M.Zhou (2000).
Structural basis of SNT PTB domain interactions with distinct neurotrophic receptors.
  Mol Cell, 6, 921-929.
PDB code: 1xr0
10747019 C.Zwahlen, S.C.Li, L.E.Kay, T.Pawson, and J.D.Forman-Kay (2000).
Multiple modes of peptide recognition by the PTB domain of the cell fate determinant Numb.
  EMBO J, 19, 1505-1515.
PDB code: 1ddm
10970839 K.Hamada, T.Shimizu, T.Matsui, S.Tsukita, and T.Hakoshima (2000).
Structural basis of the membrane-targeting and unmasking mechanisms of the radixin FERM domain.
  EMBO J, 19, 4449-4462.
PDB codes: 1gc6 1gc7
10847681 M.A.Pearson, D.Reczek, A.Bretscher, and P.A.Karplus (2000).
Structure of the ERM protein moesin reveals the FERM domain fold masked by an extended actin binding tail domain.
  Cell, 101, 259-270.
PDB code: 1ef1
10037694 A.Farooq, O.Plotnikova, L.Zeng, and M.M.Zhou (1999).
Phosphotyrosine binding domains of Shc and insulin receptor substrate 1 recognize the NPXpY motif in a thermodynamically distinct manner.
  J Biol Chem, 274, 6114-6121.  
10610414 B.Margolis, J.P.Borg, S.Straight, and D.Meyer (1999).
The function of PTB domain proteins.
  Kidney Int, 56, 1230-1237.  
  10461172 B.Margolis (1999).
The PTB Domain: The Name Doesn't Say It All.
  Trends Endocrinol Metab, 10, 262-267.  
  10454216 I.Galetic, M.Andjelkovic, R.Meier, D.Brodbeck, J.Park, and B.A.Hemmings (1999).
Mechanism of protein kinase B activation by insulin/insulin-like growth factor-1 revealed by specific inhibitors of phosphoinositide 3-kinase--significance for diabetes and cancer.
  Pharmacol Ther, 82, 409-425.  
10607674 J.D.Forman-Kay, and T.Pawson (1999).
Diversity in protein recognition by PTB domains.
  Curr Opin Struct Biol, 9, 690-695.  
10338211 K.E.Prehoda, D.J.Lee, and W.A.Lim (1999).
Structure of the enabled/VASP homology 1 domain-peptide complex: a key component in the spatial control of actin assembly.
  Cell, 97, 471-480.
PDB code: 1evh
10358772 K.Nelms, A.D.Keegan, J.Zamorano, J.J.Ryan, and W.E.Paul (1999).
The IL-4 receptor: signaling mechanisms and biologic functions.
  Annu Rev Immunol, 17, 701-738.  
10508618 N.Jones, and D.J.Dumont (1999).
Recruitment of Dok-R to the EGF receptor through its PTB domain is required for attenuation of Erk MAP kinase activation.
  Curr Biol, 9, 1057-1060.  
10411883 S.Dhe-Paganon, E.A.Ottinger, R.T.Nolte, M.J.Eck, and S.E.Shoelson (1999).
Crystal structure of the pleckstrin homology-phosphotyrosine binding (PH-PTB) targeting region of insulin receptor substrate 1.
  Proc Natl Acad Sci U S A, 96, 8378-8383.
PDB code: 1qqg
9660748 H.Xu, K.W.Lee, and M.Goldfarb (1998).
Novel recognition motif on fibroblast growth factor receptor mediates direct association and activation of SNT adapter proteins.
  J Biol Chem, 273, 17987-17990.  
9545332 H.Y.Wang, J.Zamorano, and A.D.Keegan (1998).
A role for the insulin-interleukin (IL)-4 receptor motif of the IL-4 receptor alpha-chain in regulating activation of the insulin receptor substrate 2 and signal transducer and activator of transcription 6 pathways. Analysis by mutagenesis.
  J Biol Chem, 273, 9898-9905.  
9697832 K.Nelms, A.L.Snow, J.Hu-Li, and W.E.Paul (1998).
FRIP, a hematopoietic cell-specific rasGAP-interacting protein phosphorylated in response to cytokine stimulation.
  Immunity, 9, 13-24.  
9838094 M.J.Bottomley, K.Salim, and G.Panayotou (1998).
Phospholipid-binding protein domains.
  Biochim Biophys Acta, 1436, 165-183.  
  9687374 M.S.Jurica, and B.L.Stoddard (1998).
Mind your B's and R's: bacterial chemotaxis, signal transduction and protein recognition.
  Structure, 6, 809-813.  
9660863 R.G.Kibbey, J.Rizo, L.M.Gierasch, and R.G.Anderson (1998).
The LDL receptor clustering motif interacts with the clathrin terminal domain in a reverse turn conformation.
  J Cell Biol, 142, 59-67.  
9552154 S.Alberti (1998).
A phosphoinositide-binding sequence is shared by PH domain target molecules--a model for the binding of PH domains to proteins.
  Proteins, 31, 1-9.  
9628482 S.Djordjevic, and A.M.Stock (1998).
Chemotaxis receptor recognition by protein methyltransferase CheR.
  Nat Struct Biol, 5, 446-450.
PDB code: 1bc5
9009273 B.W.Howell, F.B.Gertler, and J.A.Cooper (1997).
Mouse disabled (mDab1): a Src binding protein implicated in neuronal development.
  EMBO J, 16, 121-132.  
9434904 D.Cowburn (1997).
Peptide recognition by PTB and PDZ domains.
  Curr Opin Struct Biol, 7, 835-838.  
9100005 E.T.Olejniczak, M.M.Zhou, and S.W.Fesik (1997).
Changes in the NMR-derived motional parameters of the insulin receptor substrate 1 phosphotyrosine binding domain upon binding to an interleukin 4 receptor phosphopeptide.
  Biochemistry, 36, 4118-4124.  
9241420 J.Kuriyan, and D.Cowburn (1997).
Modular peptide recognition domains in eukaryotic signaling.
  Annu Rev Biophys Biomol Struct, 26, 259-288.  
9204876 J.Smith-Hall, S.Pons, M.E.Patti, D.J.Burks, L.Yenush, X.J.Sun, C.R.Kahn, and M.F.White (1997).
The 60 kDa insulin receptor substrate functions like an IRS protein (pp60IRS3) in adipose cells.
  Biochemistry, 36, 8304-8310.  
9268346 L.E.Rameh, A.Arvidsson, K.L.Carraway, A.D.Couvillon, G.Rathbun, A.Crompton, B.VanRenterghem, M.P.Czech, K.S.Ravichandran, S.J.Burakoff, D.S.Wang, C.S.Chen, and L.C.Cantley (1997).
A comparative analysis of the phosphoinositide binding specificity of pleckstrin homology domains.
  J Biol Chem, 272, 22059-22066.  
9207069 S.C.Li, Z.Songyang, S.J.Vincent, C.Zwahlen, S.Wiley, L.Cantley, L.E.Kay, J.Forman-Kay, and T.Pawson (1997).
High-affinity binding of the Drosophila Numb phosphotyrosine-binding domain to peptides containing a Gly-Pro-(p)Tyr motif.
  Proc Natl Acad Sci U S A, 94, 7204-7209.  
  9667855 S.E.Shoelson (1997).
SH2 and PTB domain interactions in tyrosine kinase signal transduction.
  Curr Opin Chem Biol, 1, 227-234.  
  9032245 S.Giorgetti-Peraldi, E.Ottinger, G.Wolf, B.Ye, T.R.Burke, and S.E.Shoelson (1997).
Cellular effects of phosphotyrosine-binding domain inhibitors on insulin receptor signaling and trafficking.
  Mol Cell Biol, 17, 1180-1188.  
9321393 Z.Zhang, C.H.Lee, V.Mandiyan, J.P.Borg, B.Margolis, J.Schlessinger, and J.Kuriyan (1997).
Sequence-specific recognition of the internalization motif of the Alzheimer's amyloid precursor protein by the X11 PTB domain.
  EMBO J, 16, 6141-6150.
PDB codes: 1aqc 1x11
  8805586 D.Cowburn (1996).
Adaptors and integrators.
  Structure, 4, 1005-1008.  
8810315 M.J.Hart, S.Sharma, N.elMasry, R.G.Qiu, P.McCabe, P.Polakis, and G.Bollag (1996).
Identification of a novel guanine nucleotide exchange factor for the Rho GTPase.
  J Biol Chem, 271, 25452-25458.  
8943228 S.C.Li, K.M.Lai, G.D.Gish, W.E.Parris, P.van der Geer, J.Forman-Kay, and T.Pawson (1996).
Characterization of the phosphotyrosine-binding domain of the Drosophila Shc protein.
  J Biol Chem, 271, 31855-31862.  
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.