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PDBsum entry 1hrf
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Growth factor
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PDB id
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1hrf
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References listed in PDB file
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Key reference
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Title
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Solution structure of the epidermal growth factor-Like domain of heregulin-Alpha, A ligand for p180erbb-4.
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Authors
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K.Nagata,
D.Kohda,
H.Hatanaka,
S.Ichikawa,
S.Matsuda,
T.Yamamoto,
A.Suzuki,
F.Inagaki.
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Ref.
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Embo J, 1994,
13,
3517-3523.
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PubMed id
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Note In the PDB file this reference is
annotated as "TO BE PUBLISHED".
The citation details given above were identified by an automated
search of PubMed on title and author
names, giving a
percentage match of
96%.
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Abstract
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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.
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