1hre
From Proteopedia
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|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1hrf|1HRF]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1hre FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hre OCA], [http://www.ebi.ac.uk/pdbsum/1hre PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1hre RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==Overview== | ||
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. | 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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| - | ==Disease== | ||
| - | Known diseases associated with this structure: Fibromatosis, gingival, 2 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=605544 605544]], Schizophrenia, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=142445 142445]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: growth factor]] | [[Category: growth factor]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 21:09:27 2008'' |
Revision as of 18:09, 30 March 2008
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| Related: | 1HRF
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
SOLUTION STRUCTURE OF THE EPIDERMAL GROWTH FACTOR-LIKE DOMAIN OF HEREGULIN-ALPHA, A LIGAND FOR P180ERB4
Overview
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 Structure
1HRE is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
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 Sun Mar 30 21:09:27 2008
