Biology:Bone sialoprotein

From HandWiki
Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example


Bone sialoprotein (BSP) is a component of mineralized tissues such as bone, dentin, cementum and calcified cartilage. BSP is a significant component of the bone extracellular matrix and has been suggested to constitute approximately 8% of all non-collagenous proteins found in bone and cementum.[1] BSP, a SIBLING protein, was originally isolated from bovine cortical bone as a 23-kDa glycopeptide with high sialic acid content.[2][3]

The human variant of BSP is called bone sialoprotein 2 also known as cell-binding sialoprotein or integrin-binding sialoprotein and is encoded by the IBSP gene.[4]

Structure

Native BSP has an apparent molecular weight of 60-80 kDa based on SDS-PAGE, which is a considerable deviation from the predicted weight (based on cDNA sequence) of approximately 33 kDa.[5] The mammalian BSP cDNAs encode for proteins averaging 317 amino acids, which includes the 16-residue preprotein secretory signal peptide. Among the mammalian cDNAs currently characterized, there is an approximate 45% conservation of sequence identity and a further 10-23% conservative substitution. The protein is highly acidic (pKa of ~ 3.9)[6] and contains a large amount of Glu residues, constituting ~22% of the total amino acid.

Secondary structure prediction and hydrophobicity analyses suggest that the primary sequence of BSP has an open, flexible structure with the potential to form regions of α-helix and some β-sheet.[7] However, the majority of studies have demonstrated that BSP has no α-helical or β-sheet structure by 1D NMR[6][8] and circular dichroism.[9] Analysis of native protein by electron microscopy confirm that the protein has an extended structure approximately 40 nm in length.[10] This flexible conformation suggests that the protein has few structural domains, however it has been suggested that there may be several spatially segmented functional domains including a hydrophobic collagen-binding domain (rattus norvegicus residues 36–57),[11] a hydroxyapatite-nucleating region of contiguous glutamic acid residues (rattus norvegicus residues 78–85, 155–164)[9] and a classical integrin-binding motif (RGD) near the C-terminal (rattus norvegicus residues 288–291).

BSP has been demonstrated to be extensively post-translationally modified, with carbohydrates and other modifications comprising approximately 50% of the molecular weight of the native protein.[12][13] These modifications, which include N- and O-linked glycosylation, tyrosine sulfation and serine and threonine phosphorylation, make the protein highly heterogeneous.

A 3D model of human bone sialoprotein has been developed using molecular modelling techniques, as shown in the picture above. The model suggests that the protein provides a flexible template for the rapid self-assembly of calcium and phosphate ions, so nucleating the growth of hydroxyapatite crystals.[14]

Function

The amount of BSP in bone and dentin is roughly equal,[15] however the function of BSP in these mineralized tissues is not known. One possibility is that BSP acts as a nucleus for the formation of the first apatite crystals.[16] As the apatite forms along the collagen fibres within the extracellular matrix, BSP could then help direct, redirect or inhibit the crystal growth.

Additional roles of BSP are angiogenesis and protection from complement-mediated cell lysis. Regulation of the BSP gene is important to bone matrix mineralization and tumor growth in bone.[17]

References

  1. ↑ "Human bone sialoprotein. Deduced protein sequence and chromosomal localization". J. Biol. Chem. 265 (4): 2347–51. February 1990. doi:10.1016/S0021-9258(19)39982-X. PMID 2404984. 
  2. ↑ "The physical properties of a glycoprotein from bovine cortical bone (bone sialoprotein)". Biochim. Biophys. Acta 101 (3): 327–35. November 1965. doi:10.1016/0926-6534(65)90011-4. PMID 5862222. 
  3. ↑ Herring GM (February 1964). "Comparison of bovine bone sialoprotein and serum orosomucoid". Nature 201 (4920): 709. doi:10.1038/201709a0. PMID 14139700. Bibcode: 1964Natur.201..709H. 
  4. ↑ "The human bone sialoprotein gene (IBSP): genomic localization and characterization". Genomics 17 (2): 408–15. August 1993. doi:10.1006/geno.1993.1340. PMID 8406493. https://zenodo.org/record/1229586. 
  5. ↑ "Matrix sialoprotein of developing bone". J. Biol. Chem. 258 (20): 12723–7. October 1983. doi:10.1016/S0021-9258(17)44236-0. PMID 6355090. 
  6. ↑ 6.0 6.1 "Characterization of native and recombinant bone sialoprotein: delineation of the mineral-binding and cell adhesion domains and structural analysis of the RGD domain". J. Bone Miner. Res. 12 (8): 1210–22. August 1997. doi:10.1359/jbmr.1997.12.8.1210. PMID 9258751. 
  7. ↑ "Characterization of porcine bone sialoprotein: primary structure and cellular expression". Matrix 13 (6): 431–40. November 1993. doi:10.1016/s0934-8832(11)80109-5. PMID 8309422. 
  8. ↑ "Flexible structures of SIBLING proteins, bone sialoprotein, and osteopontin". Biochem. Biophys. Res. Commun. 280 (2): 460–5. January 2001. doi:10.1006/bbrc.2000.4146. PMID 11162539. https://zenodo.org/record/1229530. 
  9. ↑ 9.0 9.1 "Delineation of the hydroxyapatite-nucleating domains of bone sialoprotein". J. Biol. Chem. 278 (10): 7949–55. March 2003. doi:10.1074/jbc.M211915200. PMID 12493752. 
  10. ↑ "The primary structure of a cell-binding bone sialoprotein". J. Biol. Chem. 263 (36): 19430–2. December 1988. doi:10.1016/S0021-9258(19)77651-0. PMID 3198635. 
  11. ↑ "Identification of the type I collagen-binding domain of bone sialoprotein and characterization of the mechanism of interaction". J. Biol. Chem. 280 (14): 13487–92. April 2005. doi:10.1074/jbc.M408923200. PMID 15703183. 
  12. ↑ "Keratan sulfate proteoglycan in rabbit compact bone is bone sialoprotein II". J. Biol. Chem. 262 (21): 10206–11. July 1987. doi:10.1016/S0021-9258(18)61099-3. PMID 2956253. 
  13. ↑ "Bone sialoprotein". Crit. Rev. Oral Biol. Med. 10 (1): 79–98. 1999. doi:10.1177/10454411990100010401. PMID 10759428. 
  14. ↑ "A structural and functional model for human bone sialoprotein". J. Mol. Graph. Model. 39: 108–117. 2013. doi:10.1016/j.jmgm.2012.10.007. PMID 23261880. http://nrl.northumbria.ac.uk/10903/1/structural_and_functional.pdf. 
  15. ↑ "A comparative study of sialic acid-rich proteins in rat bone and dentin". Eur. J. Oral Sci. 109 (2): 133–41. April 2001. doi:10.1034/j.1600-0722.2001.00001.x. PMID 11347657. 
  16. ↑ "Modulation of crystal formation by bone phosphoproteins: role of glutamic acid-rich sequences in the nucleation of hydroxyapatite by bone sialoprotein". Biochem. J. 302 ( Pt 1) (Pt 1): 175–9. August 1994. doi:10.1042/bj3020175. PMID 7915111. 
  17. ↑ Ogata Y (April 2008). "Bone sialoprotein and its transcriptional regulatory mechanism". Journal of Periodontal Research 43 (2): 127–35. doi:10.1111/j.1600-0765.2007.01014.x. PMID 18302613. 

External links

Further reading



Retrieved from "https://handwiki.org/wiki/index.php?title=Biology:Bone_sialoprotein&oldid=3527023"