Figure 1

This picture represents the structure of BMP and its receptors. (a) The snapshot of BMP7/OP1 from uniprotKB/Swiss-Prot (Accession: P18075). Genomic location on 20q13 (chr20:55,746,015–55,841,178), size: 95,164 bp and code for 7 exon (UCSC Genome Browser ID: BMP7_HUMAN). OP1 is synthesized by osteoblasts as 431 amino acid peptides (Mw-49313 Da) precursor that is consist of a hydrophobic secretory leader (signal peptide at the N-terminus domain 1AA–29AA) and a pro-peptide sequences (non-conserved domain 30AA–292AA) joined to the mature region bone morphogenetic protein 7 (C-terminus domain 293AA–431AA). The displayed sequence is further processed into a mature form. Post-translational modifications (UP) sites are i.e.; glycosylation at Asn187, Asn302, Asn321 and Asn372, and Lys162 is the ubiquitination site, and 395AA site is for interchain disulphide bond formation. (b) Butterfly-shape crystal structure of human bone morphogenetic protein 2 (RCSB PDB entry 3BMP) from X-ray diffraction with resolution of 2.70 Å. Compound: 1 polymer, 1 ligand ((4S)-2-methyl-2, 4-pentanediol (C₆H₁₄O₂)). The Jmol 3D cartoon shows two BMP2 subunit (Red and Blue) having wrist and knuckle epitopes for binding receptors. (c) A typical TGF-β/BMP consists of a cysteine knot motif with two pairs of antiparallel β-strands (fingers) extending from a α-helix (‘wrist’ region). The β-strands are curved to form both a concave and convex surface for receptor interaction. (d) Binding of BMP2 to BMPRII and BMPRIA receptors. Type I and type II receptors are glycoproteins of approximately 55 and 70 kDa, respectively. Side view (upper panel) and top view (lower panel) are shown. The ribbon diagram of hypothetical BMP2/BMPRIA/BMPRII ternary complex in the cell membrane is shown. BMP-2 has an elongated structure and binds to BMPRIA and BMPRII through wrist and knuckle epitopes, respectively. The structure of BMPRII was superposed onto that of ActR-II in the ternary complex containing BMP2, BMPRIA and ActR-II (Protein Data Bank entry 2GOO). Subunits of the BMP-2 dimer are shown in green and yellow. The extracellular domains of BMPR-IA and BMPR-II are shown in red and blue, respectively.⁴⁵ (e) Structure of the ternary signaling complex of a TGF-β super family member. Ternary Complex of BMP2 binds to BMPR-IA and ActRII (PDB ID: 2GOO). The Jmol 3D shows the color subunit ternary BMP2 and BMPRs complex backbone in surface solvent accessible manner with yellow SS bonds and red H-bonds.