PDBsum entry 1es7

Cytokine

PDB id: 1es7

Contents

Protein chains

104 a.a. *

83 a.a. *

Waters ×82

* Residue conservation analysis

PDB id:

1es7

Name:

Cytokine

Title:

Complex between bmp-2 and two bmp receptor ia ectodomains

Structure:

Bone morphogenetic protein-2. Chain: a, c. Synonym: bmp-2. Engineered: yes. Bone morphogenetic protein receptor ia. Chain: b, d. Fragment: extracellular domain. Synonym: alk-3. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Tetramer (from PQS)

Resolution:

2.90Å R-factor: 0.191 R-free: 0.229

Authors:

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

Key ref:

T.Kirsch et al. (2000). Crystal structure of the BMP-2-BRIA ectodomain complex. Nat Struct Biol, 7, 492-496. PubMed id: 10881198 DOI: 10.1038/75903

Date:

07-Apr-00 Release date: 07-Oct-00

Protein chains

P12643  (BMP2_HUMAN) -  Bone morphogenetic protein 2 from Homo sapiens

Seq: 396 a.a.

Struc: 104 a.a.

Protein chains

P36894  (BMR1A_HUMAN) -  Bone morphogenetic protein receptor type-1A from Homo sapiens

Seq: 532 a.a.

Struc: 83 a.a.

Enzyme reactions

• Enzyme class: Chains B, D: E.C.2.7.11.30 - receptor protein serine/threonine kinase.
• Reaction:
  1. L-seryl-[receptor-protein] + ATP = O-phospho-L-seryl-[receptor- protein] + ADP + H⁺
  2. L-threonyl-[receptor-protein] + ATP = O-phospho-L-threonyl-[receptor- protein] + ADP + H⁺

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1038/75903

Nat Struct Biol 7:492-496 (2000)

PubMed id: 10881198

Crystal structure of the BMP-2-BRIA ectodomain complex.

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

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.

Selected figure(s)

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.

Figures were selected by an automated process.