1NUN

Crystal Structure Analysis of the FGF10-FGFR2b Complex

1NUN の概要

• エントリーDOI: 10.2210/pdb1nun/pdb
• 分子名称: Fibroblast growth factor-10, fibroblast growth factor receptor 2 isoform 2, SULFATE ION, ... (5 entities in total)
• 機能のキーワード: beta-trefoil fold, immunoglobulin-like domain, hormone-growth factor-membrane protein complex, hormone/growth factor/membrane protein
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Secreted (Potential): O15520; Cell membrane; Single-pass type I membrane protein. Isoform 14: Secreted. Isoform 19: Secreted: P21802
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 44492.87

構造登録者

Yeh, B.K.,Igarashi, M.,Eliseenkova, A.V.,Plotnikov, A.N.,Sher, I.,Ron, D.,Aaronson, S.A.,Mohammadi, M. (登録日: 2003-01-31, 公開日: 2003-02-11, 最終更新日: 2024-10-16)

主引用文献

Yeh, B.K.,Igarashi, M.,Eliseenkova, A.V.,Plotnikov, A.N.,Sher, I.,Ron, D.,Aaronson, S.A.,Mohammadi, M.
Structural basis by which alternative splicing confers specificity in fibroblast growth factor receptors.
Proc.Natl.Acad.Sci.USA, 100:2266-2271, 2003

PubMed Abstract: 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.

PubMed: 12591959
DOI: 10.1073/pnas.0436500100

実験手法

X-RAY DIFFRACTION (2.9 Å)