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| | ==Solution structure and dynamics of the EGF/TGF-alpha chimera T1E== | | ==Solution structure and dynamics of the EGF/TGF-alpha chimera T1E== |
| - | <StructureSection load='1p9j' size='340' side='right'caption='[[1p9j]], [[NMR_Ensembles_of_Models | 36 NMR models]]' scene=''> | + | <StructureSection load='1p9j' size='340' side='right'caption='[[1p9j]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1p9j]] 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=1P9J OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1P9J FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1p9j]] 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=1P9J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1P9J FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TGF-alpha and EGF ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | </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=1p9j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1p9j OCA], [https://pdbe.org/1p9j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1p9j RCSB], [https://www.ebi.ac.uk/pdbsum/1p9j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1p9j ProSAT]</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=1p9j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1p9j OCA], [http://pdbe.org/1p9j PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1p9j RCSB], [http://www.ebi.ac.uk/pdbsum/1p9j PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1p9j ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Disease == |
| | + | [https://www.uniprot.org/uniprot/EGF_HUMAN EGF_HUMAN] Defects in EGF are the cause of hypomagnesemia type 4 (HOMG4) [MIM:[https://omim.org/entry/611718 611718]; also known as renal hypomagnesemia normocalciuric. HOMG4 is a disorder characterized by massive renal hypomagnesemia and normal levels of serum calcium and calcium excretion. Clinical features include seizures, mild-to mederate psychomotor retardation, and brisk tendon reflexes.<ref>PMID:17671655</ref> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TGFA_HUMAN TGFA_HUMAN]] TGF alpha is a mitogenic polypeptide that is able to bind to the EGF receptor/EGFR and to act synergistically with TGF beta to promote anchorage-independent cell proliferation in soft agar. | + | [https://www.uniprot.org/uniprot/EGF_HUMAN EGF_HUMAN] EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. Magnesiotropic hormone that stimulates magnesium reabsorption in the renal distal convoluted tubule via engagement of EGFR and activation of the magnesium channel TRPM6.<ref>PMID:17671655</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Ingen, H Van]]
| + | [[Category: Stortelers C]] |
| - | [[Category: Leeuwen, J E.Van]]
| + | [[Category: Van Ingen H]] |
| - | [[Category: Stortelers, C]] | + | [[Category: Van Leeuwen JE]] |
| - | [[Category: Vuister, G W]] | + | [[Category: Van Zoelen EJ]] |
| - | [[Category: Walma, T]] | + | [[Category: Vuister GW]] |
| - | [[Category: Wingens, M]]
| + | [[Category: Walma T]] |
| - | [[Category: Zoelen, E J.Van]] | + | [[Category: Wingens M]] |
| - | [[Category: Chimera]] | + | |
| - | [[Category: Egf]] | + | |
| - | [[Category: Erbb1]] | + | |
| - | [[Category: Erbb3]]
| + | |
| - | [[Category: Hormone-growth factor complex]]
| + | |
| - | [[Category: Tgf-alpha]]
| + | |
| Structural highlights
Disease
EGF_HUMAN Defects in EGF are the cause of hypomagnesemia type 4 (HOMG4) [MIM:611718; also known as renal hypomagnesemia normocalciuric. HOMG4 is a disorder characterized by massive renal hypomagnesemia and normal levels of serum calcium and calcium excretion. Clinical features include seizures, mild-to mederate psychomotor retardation, and brisk tendon reflexes.[1]
Function
EGF_HUMAN EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. Magnesiotropic hormone that stimulates magnesium reabsorption in the renal distal convoluted tubule via engagement of EGFR and activation of the magnesium channel TRPM6.[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
Various chimeras of the ErbB1-specific ligands epidermal growth factor (EGF) and transforming growth factor-alpha (TGFalpha) display an enlarged repertoire as activators of ErbB2.ErbB3 heterodimers. Mutational analysis indicated that particularly residues in the N terminus and B-loop region of these ligands are involved in the broadened receptor specificity. In order to understand the receptor specificity of T1E, a chimeric ligand constructed by the introduction of the linear N-terminal region of TGFalpha into EGF, we determined in this study the solution structure and dynamics of T1E by multidimensional NMR analysis. Subsequently, we studied the structural characteristics of T1E binding to both ErbB1 and ErbB3 by superposition modeling of its structure on the known crystal structures of ErbB3 and liganded ErbB1 complexes. The results show that the overall structure of T1E in solution is very similar to that of native EGF and TGFalpha but that its N terminus shows an extended structure that is appropriately positioned to form a triple beta-sheet with the large antiparallel beta-sheet in the B-loop region. This conformational effect of the N terminus together with the large overall flexibility of T1E, as determined by 15N NMR relaxation analysis, may be a facilitative property for its broad receptor specificity. The structural superposition models indicate that hydrophobic and electrostatic interactions of the N terminus and B-loop of T1E are particularly important for its binding to ErbB3.
Structural analysis of an epidermal growth factor/transforming growth factor-alpha chimera with unique ErbB binding specificity.,Wingens M, Walma T, van Ingen H, Stortelers C, van Leeuwen JE, van Zoelen EJ, Vuister GW J Biol Chem. 2003 Oct 3;278(40):39114-23. Epub 2003 Jul 16. PMID:12869572[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Groenestege WM, Thebault S, van der Wijst J, van den Berg D, Janssen R, Tejpar S, van den Heuvel LP, van Cutsem E, Hoenderop JG, Knoers NV, Bindels RJ. Impaired basolateral sorting of pro-EGF causes isolated recessive renal hypomagnesemia. J Clin Invest. 2007 Aug;117(8):2260-7. PMID:17671655 doi:10.1172/JCI31680
- ↑ Groenestege WM, Thebault S, van der Wijst J, van den Berg D, Janssen R, Tejpar S, van den Heuvel LP, van Cutsem E, Hoenderop JG, Knoers NV, Bindels RJ. Impaired basolateral sorting of pro-EGF causes isolated recessive renal hypomagnesemia. J Clin Invest. 2007 Aug;117(8):2260-7. PMID:17671655 doi:10.1172/JCI31680
- ↑ Wingens M, Walma T, van Ingen H, Stortelers C, van Leeuwen JE, van Zoelen EJ, Vuister GW. Structural analysis of an epidermal growth factor/transforming growth factor-alpha chimera with unique ErbB binding specificity. J Biol Chem. 2003 Oct 3;278(40):39114-23. Epub 2003 Jul 16. PMID:12869572 doi:10.1074/jbc.M305603200
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