3EVS

Crystal structure of the GDF-5:BMP receptor IB complex.

3EVS の概要

• エントリーDOI: 10.2210/pdb3evs/pdb
• 関連するPDBエントリー: 1REW 1WAQ 2H62 2K3G 2QJB
• 分子名称: Growth/differentiation factor 5, Bone morphogenetic protein receptor type-1B (3 entities in total)
• 機能のキーワード: ligand-receptor complex, cystin-knot ligand; three-finger toxn fold (receptor), cleavage on pair of basic residues, cytokine, disease mutation, dwarfism, glycoprotein, growth factor, secreted, atp-binding, kinase, magnesium, manganese, membrane, metal-binding, nucleotide-binding, receptor, serine/threonine-protein kinase, transferase, transmembrane, cytokine-transferase receptor complex, cytokine/transferase receptor
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Secreted: P43026; Membrane; Single-pass type I membrane protein: P36898
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 26620.34

構造登録者

Kotzsch, A.,Mueller, T.D. (登録日: 2008-10-13, 公開日: 2009-03-10, 最終更新日: 2024-10-16)

主引用文献

Kotzsch, A.,Nickel, J.,Seher, A.,Sebald, W.,Muller, T.D.
Crystal structure analysis reveals a spring-loaded latch as molecular mechanism for GDF-5-type I receptor specificity.
Embo J., 28:937-947, 2009

PubMed Abstract: Dysregulation of growth and differentiation factor 5 (GDF-5) signalling, a member of the TGF-beta superfamily, is strongly linked to skeletal malformation. GDF-5-mediated signal transduction involves both BMP type I receptors, BMPR-IA and BMPR-IB. However, mutations in either GDF-5 or BMPR-IB lead to similar phenotypes, indicating that in chondrogenesis GDF-5 signalling seems to be exclusively mediated through BMPR-IB. Here, we present structural insights into the GDF-5:BMPR-IB complex revealing how binding specificity for BMPR-IB is generated on a molecular level. In BMPR-IB, a loop within the ligand-binding epitope functions similar to a latch allowing high-affinity binding of GDF-5. In BMPR-IA, this latch is in a closed conformation leading to steric repulsion. The new structural data now provide also a molecular basis of how phenotypically relevant missense mutations in GDF-5 might impair receptor binding and activation.

PubMed: 19229295
DOI: 10.1038/emboj.2009.37

実験手法

X-RAY DIFFRACTION (2.1 Å)