1nun: Difference between revisions
New page: left|200px<br /> <applet load="1nun" size="450" color="white" frame="true" align="right" spinBox="true" caption="1nun, resolution 2.9Å" /> '''Crystal Structure An... |
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[[Image:1nun.gif|left|200px]]<br /> | [[Image:1nun.gif|left|200px]]<br /><applet load="1nun" size="350" color="white" frame="true" align="right" spinBox="true" | ||
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'''Crystal Structure Analysis of the FGF10-FGFR2b Complex'''<br /> | '''Crystal Structure Analysis of the FGF10-FGFR2b Complex'''<br /> | ||
==Overview== | ==Overview== | ||
Binding specificity between fibroblast growth factors (FGFs) and their | 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. | ||
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
1NUN is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with SO4 and 15P as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | 1NUN is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=SO4:'>SO4</scene> and <scene name='pdbligand=15P:'>15P</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NUN OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Aaronson, S | [[Category: Aaronson, S A.]] | ||
[[Category: Eliseenkova, A | [[Category: Eliseenkova, A V.]] | ||
[[Category: Igarashi, M.]] | [[Category: Igarashi, M.]] | ||
[[Category: Mohammadi, M.]] | [[Category: Mohammadi, M.]] | ||
[[Category: Plotnikov, A | [[Category: Plotnikov, A N.]] | ||
[[Category: Ron, D.]] | [[Category: Ron, D.]] | ||
[[Category: Sher, I.]] | [[Category: Sher, I.]] | ||
[[Category: Yeh, B | [[Category: Yeh, B K.]] | ||
[[Category: 15P]] | [[Category: 15P]] | ||
[[Category: SO4]] | [[Category: SO4]] | ||
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[[Category: immunoglobulin-like domain]] | [[Category: immunoglobulin-like domain]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:10:09 2008'' | ||
Revision as of 15:10, 21 February 2008
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Crystal Structure Analysis of the FGF10-FGFR2b Complex
OverviewOverview
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.
DiseaseDisease
Known diseases associated with this structure: Aplasia of lacrimal and salivary glands OMIM:[602115], LADD syndrome OMIM:[602115]
About this StructureAbout this Structure
1NUN is a Protein complex structure of sequences from Homo sapiens with and as ligands. Full crystallographic information is available from OCA.
ReferenceReference
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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