1hre
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SOLUTION STRUCTURE OF THE EPIDERMAL GROWTH FACTOR-LIKE DOMAIN OF HEREGULIN-ALPHA, A LIGAND FOR P180ERB4
OverviewOverview
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.
DiseaseDisease
Known diseases associated with this structure: Fibromatosis, gingival, 2 OMIM:[605544], Schizophrenia, susceptibility to OMIM:[142445]
About this StructureAbout this Structure
1HRE is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Solution structure of the epidermal growth factor-like domain of heregulin-alpha, a ligand for p180erbB-4., Nagata K, Kohda D, Hatanaka H, Ichikawa S, Matsuda S, Yamamoto T, Suzuki A, Inagaki F, EMBO J. 1994 Aug 1;13(15):3517-23. PMID:8062828
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