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PDBsum entry 1hae

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protein links
Growth factor PDB id
1hae
Jmol
Contents
Protein chain
63 a.a. *
* Residue conservation analysis
PDB id:
1hae
Name: Growth factor
Title: Heregulin-alpha epidermal growth factor-like domain, nmr, 20 structures
Structure: Heregulin-alpha. Chain: a. Fragment: epidermal growth factor-like domain. Synonym: neu differentiation factor (rat), acetylcholine receptor inducing activity (chicken), glial growth factor (human), neuregulin. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562
NMR struc: 20 models
Authors: N.E.Jacobsen,N.J.Skelton,W.J.Fairbrother
Key ref:
N.E.Jacobsen et al. (1996). High-resolution solution structure of the EGF-like domain of heregulin-alpha. Biochemistry, 35, 3402-3417. PubMed id: 8639490 DOI: 10.1021/bi952626l
Date:
30-Nov-95     Release date:   11-Jul-96    
PROCHECK
Go to PROCHECK summary
 Headers
 References

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

 

 
DOI no: 10.1021/bi952626l Biochemistry 35:3402-3417 (1996)
PubMed id: 8639490  
 
 
High-resolution solution structure of the EGF-like domain of heregulin-alpha.
N.E.Jacobsen, N.Abadi, M.X.Sliwkowski, D.Reilly, N.J.Skelton, W.J.Fairbrother.
 
  ABSTRACT  
 
The solution structure of the 63-residue heregulin-alpha (HRG-alpha) epidermal growth factor (EGF)-like domain, corresponding to residues 177-239 of HRG-alpha, has been determined to high resolution using data from two-dimensional and three-dimensional homo- and heteronuclear NMR spectroscopy. The structure is based on a total of 887 internuclear distance and dihedral restraints derived from data obtained using unlabeled and uniformly 15N-labeled protein samples, at pH 4.5, 20 degrees C. A total of 20 structures were calculated using a hybrid distance geometry-simulated annealing approach with the program DGII, followed by restrained molecular dynamics using the program DISCOVER. The average maximum violations are 0.12 +/- 0.01 angstroms and 1.4 +/- 0.3 degrees for distance and dihedral restraints, respectively. The backbone (N,C(alpha),C) atomic rms distribution about the mean coordinates for residues 3-23 and 31-49 is 0.29 +/- 0/07 angstroms. The N-and C-terminal residues (1-2 and 50-63) and 24-30 are disordered. Comparison of the HRG-alpha EGF-like domain structure with the previously determined structure of human EGF [Hommel et al. (1992) J. Mol. Biol. 227, 271-282] reveals a high degree of structural similarity; excluding the N-terminal region (residues 1-13), the disordered phi-loop region (residues 24-30) that contains a three-residue insertion in HRG-alpha relative to hEGF, and the disordered C-terminal region (residues 50-63), the C(alpha) alignment between the HRG-alpha and hEGF minimized mean structures has a rms difference of approximately 1 angstrom. In HRG-alpha the N-terminal residues 2-6 form a well-defined beta strand rather than being disordered as found for hEGF. This structural difference correlates with functional data which suggest that the N-terminal region of the HRG-alpha EGF-like domain is responsible for the observed receptor specificity differences between HRG-alpha and EGF.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21437657 W.Zhao, Y.Shen, and S.Ren (2011).
Endogenous expression of Neuregulin-1 (Nrg1) as a potential modulator of prolactin (PRL) secretion in GH3 cells.
  Cell Tissue Res, 344, 313-320.  
18821747 T.Yamamoto, P.Nair, N.E.Jacobsen, P.Davis, S.W.Ma, E.Navratilova, S.Moye, J.Lai, H.I.Yamamura, T.W.Vanderah, F.Porreca, and V.J.Hruby (2008).
The importance of micelle-bound states for the bioactivities of bifunctional peptide derivatives for delta/mu opioid receptor agonists and neurokinin 1 receptor antagonists.
  J Med Chem, 51, 6334-6347.  
16825199 C.M.Warren, K.Kani, and R.Landgraf (2006).
The N-terminal domains of neuregulin 1 confer signal attenuation.
  J Biol Chem, 281, 27306-27316.  
15822127 C.Luo, L.Xu, S.Zheng, X.Luo, J.Shen, H.Jiang, X.Liu, and M.Zhou (2005).
Computational analysis of molecular basis of 1:1 interactions of NRG-1beta wild-type and variants with ErbB3 and ErbB4.
  Proteins, 59, 742-756.  
12556529 C.Stortelers, S.P.van der Woning, S.Jacobs-Oomen, M.Wingens, and E.J.van Zoelen (2003).
Selective formation of ErbB-2/ErbB-3 heterodimers depends on the ErbB-3 affinity of epidermal growth factor-like ligands.
  J Biol Chem, 278, 12055-12063.  
12869572 M.Wingens, T.Walma, H.van Ingen, C.Stortelers, J.E.van Leeuwen, E.J.van Zoelen, and G.W.Vuister (2003).
Structural analysis of an epidermal growth factor/transforming growth factor-alpha chimera with unique ErbB binding specificity.
  J Biol Chem, 278, 39114-39123.
PDB code: 1p9j
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
9477945 B.Bersch, J.F.Hernandez, D.Marion, and G.J.Arlaud (1998).
Solution structure of the epidermal growth factor (EGF)-like module of human complement protease C1r, an atypical member of the EGF family.
  Biochemistry, 37, 1204-1214.
PDB code: 1apq
9437429 J.Gitschier, B.Moffat, D.Reilly, W.I.Wood, and W.J.Fairbrother (1998).
Solution structure of the fourth metal-binding domain from the Menkes copper-transporting ATPase.
  Nat Struct Biol, 5, 47-54.
PDB codes: 1aw0 2aw0
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.  
  9742126 R.Pinkas-Kramarski, M.Shelly, B.C.Guarino, L.M.Wang, L.Lyass, I.Alroy, M.Alimandi, A.Kuo, J.D.Moyer, S.Lavi, M.Eisenstein, B.J.Ratzkin, R.Seger, S.S.Bacus, J.H.Pierce, G.C.Andrews, Y.Yarden, and M.Alamandi (1998).
ErbB tyrosine kinases and the two neuregulin families constitute a ligand-receptor network.
  Mol Cell Biol, 18, 6090-6101.  
9799507 S.L.Schwager, A.J.Chubb, R.R.Scholle, W.F.Brandt, C.Eckerskorn, E.D.Sturrock, and M.R.Ehlers (1998).
Phorbol ester-induced juxtamembrane cleavage of angiotensin-converting enzyme is not inhibited by a stalk containing intrachain disulfides.
  Biochemistry, 37, 15449-15456.  
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.  
9659904 G.V.Louie, W.Yang, M.E.Bowman, and S.Choe (1997).
Crystal structure of the complex of diphtheria toxin with an extracellular fragment of its receptor.
  Mol Cell, 1, 67-78.
PDB code: 1xdt
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.  
9208852 S.Burden, and Y.Yarden (1997).
Neuregulins and their receptors: a versatile signaling module in organogenesis and oncogenesis.
  Neuron, 18, 847-855.  
9105049 T.Vartanian, A.Goodearl, A.Viehöver, and G.Fischbach (1997).
Axonal neuregulin signals cells of the oligodendrocyte lineage through activation of HER4 and Schwann cells through HER2 and HER3.
  J Cell Biol, 137, 211-220.  
8901515 S.J.Freedman, D.G.Sanford, W.W.Bachovchin, B.C.Furie, J.D.Baleja, and B.Furie (1996).
Structure and function of the epidermal growth factor domain of P-selectin.
  Biochemistry, 35, 13733-13744.
PDB code: 1fsb
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.