PDBsum entry 1es7

Cytokine

PDB id: 1es7

Contents

Protein chains

104 a.a. *

83 a.a. *

Waters ×82

* Residue conservation analysis

References listed in PDB file

Key reference

Title

Crystal structure of the bmp-2-Bria ectodomain complex.

Authors

T.Kirsch, W.Sebald, M.K.Dreyer.

Ref.

Nat Struct Biol, 2000, 7, 492-496. [DOI no: 10.1038/75903]

PubMed id

10881198

Abstract

Bone morphogenetic proteins (BMPs) belong to the large transforming growth factor-beta (TGF-beta) superfamily of multifunctional cytokines. BMP-2 can induce ectopic bone and cartilage formation in adult vertebrates and is involved in central steps in early embryonal development in animals. Signaling by these cytokines requires binding of two types of transmembrane serine/threonine receptor kinase chains classified as type I and type II. Here we report the crystal structure of human dimeric BMP-2 in complex with two high affinity BMP receptor IA extracellular domains (BRIAec). The receptor chains bind to the 'wrist' epitopes of the BMP-2 dimer and contact both BMP-2 monomers. No contacts exist between the receptor domains. The model reveals the structural basis for discrimination between type I and type II receptors and the variability of receptor-ligand interactions that is seen in BMP-TGF-beta systems.

Figure 1.
Figure 1. The structure of the BMP-2 -BRIA[ec] complex. a, Side view with the membrane proximal side on the bottom and b, top view approximately along the twofold axis of the complex in a ribbon representation. The BMP monomers are colored gold and blue, the two BRIA[ec] molecules are green. Secondary structure elements, chain termini and receptor loops 1 and 3 are labeled. The 'wrist' and the putative 'knuckle' epitopes on BMP-2 are highlighted. c, Stereo view of BRIA[ec] (green) superimposed with mActRII[ec] (blue). The view is onto the palm side of the hand-like structure, which provides the binding epitope for BMP-2. Disulfide bridges are depicted in yellow and magenta for BRIA[ec] and mActRII[ec], respectively, with the same numbering as in Fig. 2. The side chain of Phe 85 in helix 1 of BRIA[ec] is shown.

Figure 4.
Figure 4. Stereo view of the hydrophobic pocket around BRIA[ec] residue Phe 85. Receptor residues Phe 85 -Cys 87 are depicted in green, BMP-2[A] residues Asn 59 -Val 63 in blue, and BMP-2[B] residues Trp 28 -Ile 32, Met 89 -Leu 92, and Tyr 103 -Met 106 in gold. The 2F[o] - F[c] electron density map was calculated omitting receptor helix residues 80 -87 and is contoured at 1.0 .

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (2000, 7, 492-496) copyright 2000.

Secondary reference #1

Title

Crystal structure of human bone morphogenetic protein-2 at 2.7 a resolution.

Authors

C.Scheufler, W.Sebald, M.Hülsmeyer.

Ref.

J Mol Biol, 1999, 287, 103-115. [DOI no: 10.1006/jmbi.1999.2590]

PubMed id

10074410

Figure 2.
Figure 2. Stereoview of the folding topology of the native BMP-2 dimer: α-helices are indicated as spiral, β-strands as arrow, disulfide bridges are shown as green sticks. The subunits are color-coded blue and orange, respectively. The interactions that are responsible for dimer formation between helix α3 and the β-strands of the other subunit are clearly visible. cis-Pro35 and Phe41 are indicated in dark gray. The unique β-strand β5a is located near helix α3. The Figure was produced with Ribbons [Carson and Bugg 1986].

Figure 5.
Figure 5. Superposition of TGF-β family proteins. For clarity only monomers of each protein are displayed: BMP-2 in blue, BMP-7 in red, TGF-β2 in orange, TGF-β3 in yellow. The smoothing of the C^α trace was disabled to emphasize the differences in the structure models.

The above figures are reproduced from the cited reference with permission from Elsevier

Secondary reference #2

Title

Isolation of recombinant bmp receptor ia ectodomain and its 2:1 complex with bmp-2.

Authors

T.Kirsch, J.Nickel, W.Sebald.

Ref.

Febs Lett, 2000, 468, 215-219.

PubMed id

10692589