1p9j

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[[Image:1p9j.gif|left|200px]]
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[[Image:1p9j.png|left|200px]]
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{{STRUCTURE_1p9j| PDB=1p9j | SCENE= }}
{{STRUCTURE_1p9j| PDB=1p9j | SCENE= }}
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'''Solution structure and dynamics of the EGF/TGF-alpha chimera T1E'''
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===Solution structure and dynamics of the EGF/TGF-alpha chimera T1E===
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==Overview==
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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.
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(as it appears on PubMed at http://www.pubmed.gov), where 12869572 is the PubMed ID number.
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{{ABSTRACT_PUBMED_12869572}}
==About this Structure==
==About this Structure==
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1P9J 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=1P9J OCA].
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1P9J is a [[Single protein]] structure of sequence from [http://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].
==Reference==
==Reference==
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[[Category: Erbb3]]
[[Category: Erbb3]]
[[Category: Tgf-alpha]]
[[Category: Tgf-alpha]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 04:51:13 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 08:43:30 2008''

Revision as of 05:43, 29 July 2008

Template:STRUCTURE 1p9j

Solution structure and dynamics of the EGF/TGF-alpha chimera T1E

Template:ABSTRACT PUBMED 12869572

About this Structure

1P9J is a Single protein structure of sequence from Homo sapiens. Full experimental information is available from OCA.

Reference

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

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