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PDB:1ES7

Protein Name

Bone morphogenetic protein 2 (BMP2)/BRIA ectodomain complex

Species

Homo sapiens (human)

Biological Context

The transforming growth factor-beta (TGF-beta) superfamily of proteins consists of structurally related, homodimeric, secreted proteins that act as ligands to various receptors and thus regulate a large number of biological functions. TGF-beta like ligands include bone morphogenetic(morphogenic) proteins (BMPs), activins, inhibins, glial-cell derived growth factors and the TGF- betas themselves. Apart from regulating pattern formation during development, these proteins influence cell proliferation, differentiation, extracellular matrix production and cell death. They act mainly through two types of structurally similar, transmembrane receptors typeI and typeII, that have a serine-threonine kinase domain on the cytosolic side of the plasma membrane. Each member of the TGF-beta superfamily binds to a characteristic combination of typeI and typeII receptors that are required for the initiation of intracellular signaling. BMP-2, a member of the BMP family of proteins, is known to be involved in embryonal development in animals, and in the induction of ectopic bone and cartilage formation in adult vertebrates.

Structure Description

1es71es7_x1es7_y

As a monomer, it forms an elongated structure with a central beta-sheet and a cystine knot at one end. The BMP-2 dimer functions by first binding, with high affinity, to two BMP receptor IA (BRIA) typeI receptors. This intermediate complex then recruits the low affinity typeII receptors which in turn phosphorylate the BRIA receptors and trigger the signaling pathway in the cell. The structure shown here is that of the intermediate complex. The complex consists of an elongated homodimer of BMP-2 bound to two BRIA molecules at symmetric binding sites. The receptors are bound at the far ends of the dimeric BMP-2 molecule and thus there are no contacts between them. Although the typeI and typeII receptors are structurally related, this structure shows the presence of a helix in the BRIA, which may be conserved across all typeI receptors.

Protein Data Bank (PDB)

References

Source

  • Kirsch, T. Sebald, W. Dreyer, M.K.; "Crystal structure of the BMP-2-BRIA ectodomain complex."; Nature Struct. Biol.; (2000) 7:492-496 PubMed:10881198.

Others

Author: Ashwini Patil


Japanese version:PDB:1ES7