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PDBsum entry 1hae
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Growth factor
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PDB id
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1hae
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Contents |
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* Residue conservation analysis
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PDB id:
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Growth factor
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Title:
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Heregulin-alpha epidermal growth factor-like domain, nmr, 20 structures
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Structure:
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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
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562
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NMR struc:
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20 models
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Authors:
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N.E.Jacobsen,N.J.Skelton,W.J.Fairbrother
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Key ref:
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N.E.Jacobsen
et al.
(1996).
High-resolution solution structure of the EGF-like domain of heregulin-alpha.
Biochemistry,
35,
3402-3417.
PubMed id:
DOI:
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Date:
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30-Nov-95
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Release date:
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11-Jul-96
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PROCHECK
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Headers
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References
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Q02297
(NRG1_HUMAN) -
Pro-neuregulin-1, membrane-bound isoform from Homo sapiens
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Seq:
Struc:
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640 a.a.
63 a.a.
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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DOI no:
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Biochemistry
35:3402-3417
(1996)
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PubMed id:
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High-resolution solution structure of the EGF-like domain of heregulin-alpha.
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N.E.Jacobsen,
N.Abadi,
M.X.Sliwkowski,
D.Reilly,
N.J.Skelton,
W.J.Fairbrother.
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ABSTRACT
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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.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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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.
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Cell Tissue Res,
344,
313-320.
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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.
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J Med Chem,
51,
6334-6347.
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C.M.Warren,
K.Kani,
and
R.Landgraf
(2006).
The N-terminal domains of neuregulin 1 confer signal attenuation.
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J Biol Chem,
281,
27306-27316.
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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.
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Proteins,
59,
742-756.
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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.
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J Biol Chem,
278,
12055-12063.
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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.
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J Biol Chem,
278,
39114-39123.
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PDB code:
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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.
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Cell,
110,
763-773.
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PDB code:
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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.
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Biochemistry,
37,
1204-1214.
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PDB code:
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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.
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Nat Struct Biol,
5,
47-54.
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PDB codes:
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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.
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J Biol Chem,
273,
11667-11674.
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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.
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J Biol Chem,
273,
11675-11684.
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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.
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Mol Cell Biol,
18,
6090-6101.
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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.
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Biochemistry,
37,
15449-15456.
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Y.Abe,
M.Odaka,
F.Inagaki,
I.Lax,
J.Schlessinger,
and
D.Kohda
(1998).
Disulfide bond structure of human epidermal growth factor receptor.
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J Biol Chem,
273,
11150-11157.
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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.
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EMBO J,
16,
4938-4950.
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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.
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Mol Cell,
1,
67-78.
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PDB code:
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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.
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Biochemistry,
36,
3837-3845.
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S.Burden,
and
Y.Yarden
(1997).
Neuregulins and their receptors: a versatile signaling module in organogenesis and oncogenesis.
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Neuron,
18,
847-855.
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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.
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J Cell Biol,
137,
211-220.
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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.
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Biochemistry,
35,
13733-13744.
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PDB code:
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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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Links
