1nun

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{{STRUCTURE_1nun| PDB=1nun | SCENE= }}
{{STRUCTURE_1nun| PDB=1nun | SCENE= }}
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'''Crystal Structure Analysis of the FGF10-FGFR2b Complex'''
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===Crystal Structure Analysis of the FGF10-FGFR2b Complex===
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==Overview==
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Binding specificity between fibroblast growth factors (FGFs) and their receptors (FGFRs) is essential for mammalian development and is regulated primarily by two alternatively spliced exons, IIIb ("b") and IIIc ("c"), that encode the second half of Ig-like domain 3 (D3) of FGFRs. FGF7 and FGF10 activate only the b isoform of FGFR2 (FGFR2b). Here, we report the crystal structure of the ligand-binding portion of FGFR2b bound to FGF10. Unique contacts between divergent regions in FGF10 and two b-specific loops in D3 reveal the structural basis by which alternative splicing provides FGF10-FGFR2b specificity. Structure-based mutagenesis of FGF10 confirms the importance of the observed contacts for FGF10 biological activity. Interestingly, FGF10 binding induces a previously unobserved rotation of receptor Ig domain 2 (D2) to introduce specific contacts with FGF10. Hence, both D2 and D3 of FGFR2b contribute to the exceptional specificity between FGF10 and FGFR2b. We propose that ligand-induced conformational change in FGFRs may also play an important role in determining specificity for other FGF-FGFR complexes.
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The line below this paragraph, {{ABSTRACT_PUBMED_12591959}}, adds the Publication Abstract to the page
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(as it appears on PubMed at http://www.pubmed.gov), where 12591959 is the PubMed ID number.
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{{ABSTRACT_PUBMED_12591959}}
==Disease==
==Disease==
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[[Category: Beta-trefoil fold]]
[[Category: Beta-trefoil fold]]
[[Category: Immunoglobulin-like domain]]
[[Category: Immunoglobulin-like domain]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 02:59:53 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 13:36:03 2008''

Revision as of 10:36, 29 July 2008

Image:1nun.png

Template:STRUCTURE 1nun

Contents

Crystal Structure Analysis of the FGF10-FGFR2b Complex

Template:ABSTRACT PUBMED 12591959

Disease

Known disease associated with this structure: Aplasia of lacrimal and salivary glands OMIM:[602115], LADD syndrome OMIM:[602115]

About this Structure

1NUN is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Structural basis by which alternative splicing confers specificity in fibroblast growth factor receptors., Yeh BK, Igarashi M, Eliseenkova AV, Plotnikov AN, Sher I, Ron D, Aaronson SA, Mohammadi M, Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2266-71. Epub 2003 Feb 18. PMID:12591959

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