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1nun
From Proteopedia
Contents |
Crystal Structure Analysis of the FGF10-FGFR2b Complex
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.
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
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
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 2 chains structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
- Yeh BK, Igarashi M, Eliseenkova AV, Plotnikov AN, Sher I, Ron D, Aaronson SA, Mohammadi M. Structural basis by which alternative splicing confers specificity in fibroblast growth factor receptors. Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2266-71. Epub 2003 Feb 18. PMID:12591959 doi:10.1073/pnas.0436500100
Page seeded by OCA on Wed Feb 18 06:50:07 2009
