1M4U

Crystal structure of Bone Morphogenetic Protein-7 (BMP-7) in complex with the secreted antagonist Noggin

1M4U の概要

• エントリーDOI: 10.2210/pdb1m4u/pdb
• 関連するPDBエントリー: 1BMP 1ES7 3BMP
• 分子名称: Bone Morphogenetic Protein-7, Noggin, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• 機能のキーワード: noggin, bmp antagonist, bmp-7, bone morphogenetic protein, cystine knot, hormone-growth factor complex, hormone/growth factor
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Secreted: P18075 Q13253
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 39336.98

構造登録者

Groppe, J.,Greenwald, J.,Wiater, E.,Rodriguez-Leon, J.,Economides, A.N.,Kwiatkowski, W.,Affolter, M.,Vale, W.W.,Izpisua-Belmonte, J.C.,Choe, S. (登録日: 2002-07-03, 公開日: 2002-12-18, 最終更新日: 2024-10-30)

主引用文献

Groppe, J.,Greenwald, J.,Wiater, E.,Rodriguez-Leon, J.,Economides, A.N.,Kwiatkowski, W.,Affolter, M.,Vale, W.W.,Izpisua-Belmonte, J.C.,Choe, S.
Structural Basis of BMP Signalling Inhibition by the Cystine Knot Protein Noggin
Nature, 420:636-642, 2002

PubMed Abstract: The interplay between bone morphogenetic proteins (BMPs) and their antagonists governs developmental and cellular processes as diverse as establishment of the embryonic dorsal-ventral axis, induction of neural tissue, formation of joints in the skeletal system and neurogenesis in the adult brain. So far, the three-dimensional structures of BMP antagonists and the structural basis for inactivation have remained unknown. Here we report the crystal structure of the antagonist Noggin bound to BMP-7, which shows that Noggin inhibits BMP signalling by blocking the molecular interfaces of the binding epitopes for both type I and type II receptors. The BMP-7-binding affinity of site-specific variants of Noggin is correlated with alterations in bone formation and apoptosis in chick limb development, showing that Noggin functions by sequestering its ligand in an inactive complex. The scaffold of Noggin contains a cystine (the oxidized form of cysteine) knot topology similar to that of BMPs; thus, ligand and antagonist seem to have evolved from a common ancestral gene.

PubMed: 12478285
DOI: 10.1038/nature01245

実験手法

X-RAY DIFFRACTION (2.42 Å)