1hre: Difference between revisions

Revision as of 19:09, 2 May 2008

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.

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 Page seeded by OCA on Fri May 2 19:09:34 2008

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OCA

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- {{Structure
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 '''SOLUTION STRUCTURE OF THE EPIDERMAL GROWTH FACTOR-LIKE DOMAIN OF HEREGULIN-ALPHA, A LIGAND FOR P180ERB4'''
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 [[Category: Kohda, D.]]
 [[Category: Nagata, K.]]
-[[Category: growth factor]]
+[[Category: Growth factor]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May  2 19:09:34 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 21:09:27 2008''