1hre: Difference between revisions

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-[[Image:1hre.jpg|left|200px]]
-<!--
+==SOLUTION STRUCTURE OF THE EPIDERMAL GROWTH FACTOR-LIKE DOMAIN OF HEREGULIN-ALPHA, A LIGAND FOR P180ERB4==
-The line below this paragraph, containing "STRUCTURE_1hre", creates the "Structure Box" on the page.
+<StructureSection load='1hre' size='340' side='right'caption='[[1hre]]' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[1hre]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HRE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1HRE FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
--->
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1hre FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hre OCA], [https://pdbe.org/1hre PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1hre RCSB], [https://www.ebi.ac.uk/pdbsum/1hre PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1hre ProSAT]</span></td></tr>
-{{STRUCTURE_1hre|  PDB=1hre  |  SCENE=  }}
+</table>
+== Disease ==
-'''SOLUTION STRUCTURE OF THE EPIDERMAL GROWTH FACTOR-LIKE DOMAIN OF HEREGULIN-ALPHA, A LIGAND FOR P180ERB4'''
+[https://www.uniprot.org/uniprot/NRG1_HUMAN NRG1_HUMAN] Note=A chromosomal aberration involving NRG1 produces gamma-heregulin. Translocation t(8;11) with TENM4. The translocation fuses the 5'-end of TENM4 to NRG1 (isoform 8). The product of this translocation was first thought to be an alternatively spliced isoform. Gamma-heregulin is a soluble activating ligand for the ERBB2-ERBB3 receptor complex and acts as an autocrine growth factor in a specific breast cancer cell line (MDA-MB-175). Not detected in breast carcinoma samples, including ductal, lobular, medullary, and mucinous histological types, neither in other breast cancer cell lines.
+== Function ==
+[https://www.uniprot.org/uniprot/NRG1_HUMAN NRG1_HUMAN] Direct ligand for ERBB3 and ERBB4 tyrosine kinase receptors. Concomitantly recruits ERBB1 and ERBB2 coreceptors, resulting in ligand-stimulated tyrosine phosphorylation and activation of the ERBB receptors. The multiple isoforms perform diverse functions such as inducing growth and differentiation of epithelial, glial, neuronal, and skeletal muscle cells; inducing expression of acetylcholine receptor in synaptic vesicles during the formation of the neuromuscular junction; stimulating lobuloalveolar budding and milk production in the mammary gland and inducing differentiation of mammary tumor cells; stimulating Schwann cell proliferation; implication in the development of the myocardium such as trabeculation of the developing heart. Isoform 10 may play a role in motor and sensory neuron development.<ref>PMID:1348215</ref> <ref>PMID:7902537</ref>
-==Overview==
+== Evolutionary Conservation ==
-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.
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
-==About this Structure==
+  <jmolCheckbox>
-HRE is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HRE OCA].
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hr/1hre_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
-==Reference==
+    <text>to colour the structure by Evolutionary Conservation</text>
-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:[http://www.ncbi.nlm.nih.gov/pubmed/8062828 8062828]
+  </jmolCheckbox>
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1hre ConSurf].
+<div style="clear:both"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Single protein]]
+[[Category: Large Structures]]
-[[Category: Hatanaka, H.]]
+[[Category: Hatanaka H]]
-[[Category: Ichikawa, S.]]
+[[Category: Ichikawa S]]
-[[Category: Inagaki, F.]]
+[[Category: Inagaki F]]
-[[Category: Kohda, D.]]
+[[Category: Kohda D]]
-[[Category: Nagata, K.]]
+[[Category: Nagata K]]
-[[Category: Growth factor]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May  2 19:09:34 2008''