1m4u
From Proteopedia
Crystal structure of Bone Morphogenetic Protein-7 (BMP-7) in complex with the secreted antagonist Noggin
Contents |
Overview
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.
Disease
Known disease associated with this structure: Stapes ankylosis syndrome without symphalangism OMIM:[602991], Symphalangism, proximal OMIM:[602991], Synostoses syndrome, multiple, 1 OMIM:[602991], Tarsal-carpal coalition syndrome OMIM:[602991]
About this Structure
1M4U is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structural basis of BMP signalling inhibition by the cystine knot protein Noggin., Groppe J, Greenwald J, Wiater E, Rodriguez-Leon J, Economides AN, Kwiatkowski W, Affolter M, Vale WW, Belmonte JC, Choe S, Nature. 2002 Dec 12;420(6916):636-42. PMID:12478285 Page seeded by OCA on Sat May 3 00:37:55 2008
