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PDBsum entry 1hrf
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protein links
Growth factor PDB id
1hrf

 

 

 

 

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Contents
Protein chain
67 a.a. *
* Residue conservation analysis
PDB id:
1hrf
Name: Growth factor
Title: Solution structure of the epidermal growth factor-like domain of heregulin-alpha, a ligand for p180erb4
Structure: Heregulin alpha. Chain: a. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606
NMR struc: 10 models
Authors: K.Nagata,D.Kohda,H.Hatanaka,S.Ichikawa,F.Inagaki
Key ref: K.Nagata et al. (1994). Solution structure of the epidermal growth factor-like domain of heregulin-alpha, a ligand for p180erbB-4. Embo J, 13, 3517-3523. PubMed id: 8062828
Date:
21-Jul-94     Release date:   15-Oct-94    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q02297  (NRG1_HUMAN) -  Pro-neuregulin-1, membrane-bound isoform from Homo sapiens
Seq:
Struc: 		 
Seq:
Struc: 		640 a.a.
67 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 

 
Embo J 13:3517-3523 (1994)
PubMed id: 8062828  
 
 
Solution structure of the epidermal growth factor-like domain of heregulin-alpha, a ligand for p180erbB-4.
K.Nagata, D.Kohda, H.Hatanaka, S.Ichikawa, S.Matsuda, T.Yamamoto, A.Suzuki, F.Inagaki.
 
  ABSTRACT  
 
p185erbB-2 and p180erbB-4 are epidermal growth factor (EGF) receptor-like tyrosine kinases, whose co-expression is observed in many breast carcinomas. Heregulins (HRGs), which contain an immunoglobulin unit and an EGF-like domain, bind to p180erbB-4 and activate p180erbB-4 and p185erbB-2 through transphosphorylation or receptor heterodimerization. The EGF-like domain is sufficient for the activation. Despite the sequence similarity, no cross activity is seen between the p180erbB-4 ligands (HRGs) and the p170erbB-1 ligands [EGF and transforming growth factor (TGF)-alpha]. To investigate the structural basis of receptor specificity, we have determined the solution structure of the EGF-like domain of HRG-alpha by two-dimensional 1H nuclear magnetic resonance spectroscopy and simulated annealing calculations. Though its main-chain fold is similar to those of EGF and TGF-alpha, distinctive structural features are observed on the molecular surface including an ionic cluster and hydrophobic patches, which afford HRG-alpha the specific affinity for p180erbB-4. The structure should provide a basis for the structure-activity relationship of HRGs and for the design of drugs which prevent progression of breast cancer.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20208353 K.Nagata (2010).
Studies of the structure-activity relationships of peptides and proteins involved in growth and development based on their three-dimensional structures.
  Biosci Biotechnol Biochem, 74, 462-470.  
  20198187 K.Sikic, and O.Carugo (2009).
CARON - Average RMSD of NMR structure ensembles.
  Bioinformation, 4, 132-133.  
17880034 T.Kakizawa, S.Koide-Yoshida, T.Kimura, H.Uchimura, Y.Hayashi, K.Saito, and Y.Kiso (2008).
Fmoc-based solid phase chemical synthesis of 71-meric neuregulin 1-beta1, an epidermal growth factor-like domain.
  J Pept Sci, 14, 261-266.  
12297049 T.P.Garrett, N.M.McKern, M.Lou, T.C.Elleman, T.E.Adams, G.O.Lovrecz, H.J.Zhu, F.Walker, M.J.Frenkel, P.A.Hoyne, R.N.Jorissen, E.C.Nice, A.W.Burgess, and C.W.Ward (2002).
Crystal structure of a truncated epidermal growth factor receptor extracellular domain bound to transforming growth factor alpha.
  Cell, 110, 763-773.
PDB code: 1mox
9565587 J.T.Jones, M.D.Ballinger, P.I.Pisacane, J.A.Lofgren, V.D.Fitzpatrick, W.J.Fairbrother, J.A.Wells, and M.X.Sliwkowski (1998).
Binding interaction of the heregulinbeta egf domain with ErbB3 and ErbB4 receptors assessed by alanine scanning mutagenesis.
  J Biol Chem, 273, 11667-11674.  
9565588 M.D.Ballinger, J.T.Jones, J.A.Lofgren, W.J.Fairbrother, R.W.Akita, M.X.Sliwkowski, and J.A.Wells (1998).
Selection of heregulin variants having higher affinity for the ErbB3 receptor by monovalent phage display.
  J Biol Chem, 273, 11675-11684.  
9485477 R.Landgraf, M.Pegram, D.J.Slamon, and D.Eisenberg (1998).
Cytotoxicity and specificity of directed toxins composed of diphtheria toxin and the EGF-like domain of heregulin beta1.
  Biochemistry, 37, 3220-3228.  
9556602 Y.Abe, M.Odaka, F.Inagaki, I.Lax, J.Schlessinger, and D.Kohda (1998).
Disulfide bond structure of human epidermal growth factor receptor.
  J Biol Chem, 273, 11150-11157.  
9305636 E.Tzahar, R.Pinkas-Kramarski, J.D.Moyer, L.N.Klapper, I.Alroy, G.Levkowitz, M.Shelly, S.Henis, M.Eisenstein, B.J.Ratzkin, M.Sela, G.C.Andrews, and Y.Yarden (1997).
Bivalence of EGF-like ligands drives the ErbB signaling network.
  EMBO J, 16, 4938-4950.  
9056721 G.D.Fischbach, and K.M.Rosen (1997).
ARIA: a neuromuscular junction neuregulin.
  Annu Rev Neurosci, 20, 429-458.  
9092813 M.Lohmeyer, P.M.Harrison, S.Kannan, M.DeSantis, N.J.O'Reilly, M.J.Sternberg, D.S.Salomon, and W.J.Gullick (1997).
Chemical synthesis, structural modeling, and biological activity of the epidermal growth factor-like domain of human cripto.
  Biochemistry, 36, 3837-3845.  
8816772 C.E.White, M.J.Hunter, D.P.Meininger, S.Garrod, and E.A.Komives (1996).
The fifth epidermal growth factor-like domain of thrombomodulin does not have an epidermal growth factor-like disulfide bonding pattern.
  Proc Natl Acad Sci U S A, 93, 10177-10182.  
8639490 N.E.Jacobsen, N.Abadi, M.X.Sliwkowski, D.Reilly, N.J.Skelton, and W.J.Fairbrother (1996).
High-resolution solution structure of the EGF-like domain of heregulin-alpha.
  Biochemistry, 35, 3402-3417.
PDB codes: 1hae 1haf
7721889 E.G.Barbacci, B.C.Guarino, J.G.Stroh, D.H.Singleton, K.J.Rosnack, J.D.Moyer, and G.C.Andrews (1995).
The structural basis for the specificity of epidermal growth factor and heregulin binding.
  J Biol Chem, 270, 9585-9589.  
7876251 H.S.Lu, D.Chang, J.S.Philo, K.Zhang, L.O.Narhi, N.Liu, M.Zhang, J.Sun, J.Wen, and D.Yanagihara (1995).
Studies on the structure and function of glycosylated and nonglycosylated neu differentiation factors. Similarities and differences of the alpha and beta isoforms.
  J Biol Chem, 270, 4784-4791.  
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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