1M4U

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

Summary for 1M4U

• Entry DOI: 10.2210/pdb1m4u/pdb
• Related: 1BMP 1ES7 3BMP
• Descriptor: 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)
• Functional Keywords: noggin, bmp antagonist, bmp-7, bone morphogenetic protein, cystine knot, hormone-growth factor complex, hormone/growth factor
• Biological source: Homo sapiens (human); More
• Cellular location: Secreted: P18075 Q13253
• Total number of polymer chains: 2
• Total formula weight: 39336.98

Authors

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. (deposition date: 2002-07-03, release date: 2002-12-18, Last modification date: 2024-10-30)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.42 Å)