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1hae

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Revision as of 09:01, 10 January 2018

HEREGULIN-ALPHA EPIDERMAL GROWTH FACTOR-LIKE DOMAIN, NMR, 20 STRUCTURES

Structural highlights

1hae is a 1 chain structure with sequence from Human. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	1haf
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[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

[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.^[1] ^[2]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The solution structure of the 63-residue heregulin-alpha (HRG-alpha) epidermal growth factor (EGF)-like domain, corresponding to residues 177-239 of HRG-alpha, has been determined to high resolution using data from two-dimensional and three-dimensional homo- and heteronuclear NMR spectroscopy. The structure is based on a total of 887 internuclear distance and dihedral restraints derived from data obtained using unlabeled and uniformly 15N-labeled protein samples, at pH 4.5, 20 degrees C. A total of 20 structures were calculated using a hybrid distance geometry-simulated annealing approach with the program DGII, followed by restrained molecular dynamics using the program DISCOVER. The average maximum violations are 0.12 +/- 0.01 angstroms and 1.4 +/- 0.3 degrees for distance and dihedral restraints, respectively. The backbone (N,C(alpha),C) atomic rms distribution about the mean coordinates for residues 3-23 and 31-49 is 0.29 +/- 0/07 angstroms. The N-and C-terminal residues (1-2 and 50-63) and 24-30 are disordered. Comparison of the HRG-alpha EGF-like domain structure with the previously determined structure of human EGF [Hommel et al. (1992) J. Mol. Biol. 227, 271-282] reveals a high degree of structural similarity; excluding the N-terminal region (residues 1-13), the disordered phi-loop region (residues 24-30) that contains a three-residue insertion in HRG-alpha relative to hEGF, and the disordered C-terminal region (residues 50-63), the C(alpha) alignment between the HRG-alpha and hEGF minimized mean structures has a rms difference of approximately 1 angstrom. In HRG-alpha the N-terminal residues 2-6 form a well-defined beta strand rather than being disordered as found for hEGF. This structural difference correlates with functional data which suggest that the N-terminal region of the HRG-alpha EGF-like domain is responsible for the observed receptor specificity differences between HRG-alpha and EGF.

High-resolution solution structure of the EGF-like domain of heregulin-alpha.,Jacobsen NE, Abadi N, Sliwkowski MX, Reilly D, Skelton NJ, Fairbrother WJ Biochemistry. 1996 Mar 19;35(11):3402-17. PMID:8639490^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Peles E, Bacus SS, Koski RA, Lu HS, Wen D, Ogden SG, Levy RB, Yarden Y. Isolation of the neu/HER-2 stimulatory ligand: a 44 kd glycoprotein that induces differentiation of mammary tumor cells. Cell. 1992 Apr 3;69(1):205-16. PMID:1348215
↑ Plowman GD, Green JM, Culouscou JM, Carlton GW, Rothwell VM, Buckley S. Heregulin induces tyrosine phosphorylation of HER4/p180erbB4. Nature. 1993 Dec 2;366(6454):473-5. PMID:7902537 doi:http://dx.doi.org/10.1038/366473a0
↑ Jacobsen NE, Abadi N, Sliwkowski MX, Reilly D, Skelton NJ, Fairbrother WJ. High-resolution solution structure of the EGF-like domain of heregulin-alpha. Biochemistry. 1996 Mar 19;35(11):3402-17. PMID:8639490 doi:http://dx.doi.org/10.1021/bi952626l

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1hae"

Categories: Human | Fairbrother, W J | Jacobsen, N E | Skelton, N J | Growth factor

@@ Line 1: / Line 1: @@
 ==HEREGULIN-ALPHA EPIDERMAL GROWTH FACTOR-LIKE DOMAIN, NMR, 20 STRUCTURES==
 <StructureSection load='1hae' size='340' side='right' caption='[[1hae]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
@@ Line 4: / Line 5: @@
 <table><tr><td colspan='2'>[[1hae]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HAE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1HAE FirstGlance]. <br>
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1haf|1haf]]</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1hae FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hae OCA], [http://pdbe.org/1hae PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1hae RCSB], [http://www.ebi.ac.uk/pdbsum/1hae PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1hae FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hae OCA], [http://pdbe.org/1hae PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1hae RCSB], [http://www.ebi.ac.uk/pdbsum/1hae PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1hae ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 14: / Line 15: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ha/1hae_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ha/1hae_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>

1hae

From Proteopedia

Revision as of 09:01, 10 January 2018

HEREGULIN-ALPHA EPIDERMAL GROWTH FACTOR-LIKE DOMAIN, NMR, 20 STRUCTURES

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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