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Bone sialoprotein



Integrin-binding bone sialoprotein (ibsp, bone sialoprotein, bsp, bspII, spII)
Identifiers
Symbol IBSP
Entrez 3381
HUGO 5341
OMIM 147563
RefSeq NP_004958.1
UniProt P21815
Other data
Locus Chr. 4 q21-q25

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 was originally isolated from bovine cortical bone as a 23-kDa glycopeptide with high sialic acid content, as described in separate reports by Williams and Peacocke [2] and Andrews and Herring [3] in 1965. 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 [4]. The mammalian BSP cDNAs encode for proteins averaging 327 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) [5] and contains a large amount of Glu residues, constituting ~22% of the total amino acid.

Additional recommended knowledge

Structure

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 [6]. However, the majority of studies have demonstrated that BSP has no α-helical or β-sheet structure by 1D NMR [7] [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) [12] 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 [13][14][15]. These modifications, which include N- and O-linked glycosylation, tyrosine sulfation and serine and threonine phosphorylation, make the protein highly heterogeneous.

Function

The amount of BSP in bone and dentin is roughly equal,[16] 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.[17].As the apatite forms along the collagen fibres with in the extracellular matrix, BSP could then help direct, redirect or inhibit the crystal growth.

References

  1. ^ Fisher, L.W., McBride, O.W., Termine, J.D., Young, M.F. Human bone sialoprotein. Deduced protein sequence and chromosomal localization. J. Biol. Chem. 1990 265:2347-51. PMID 2404984
  2. ^ Williams, P.A., Peacocke, A.R. The physical properties of a glycoprotein frombovine cortical bone (bone sialoprotein). Biochim. Biophys. Acta. 1965 101:327-35. PMID 5862222
  3. ^ Herring, G.M. Comparison of Bovine Bone Sialoprotein and Serum Orosomucoid. Nature 1964 201:709. PMID 14139700
  4. ^ Fisher, L.W., Whitson, S.W., Avioli, L.V., Termine, J.D. Matrix sialoprotein of developing bone. J. Biol. Chem. 1983 258:12723-7. PMID 6355090
  5. ^ Stubbs, J.T., 3rd, Mintz, K.P., Eanes, E.D., Torchia, D.A., Fisher, L.W. 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. 1997 12:1210-22. PMID 9258751
  6. ^ Shapiro, H.S., Chen, J., Wrana, J.L., Zhang, Q., Blum, M., Sodek, J. Characterization of porcine bone sialoprotein: primary structure and cellular expression. Matrix 1993 13:431-40. PMID 8309422
  7. ^ Fisher, L.W., Torchia, D.A., Fohr, B., Young, M.F., Fedarko, N.S. Flexible structures of SIBLING proteins, bone sialoprotein, and osteopontin. Biochem. Biophys. Res. Comm. 2001 280:460-5. PMID 11162539
  8. ^ Stubbs, J.T., 3rd, Mintz, K.P., Eanes, E.D., Torchia, D.A., Fisher, L.W. 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. 1997 12:1210-22. PMID: 9258751
  9. ^ Tye, C.E., Rattray, K.R., Warner, K.J., Gordon, J.A., Sodek, J., Hunter, G.K., Goldberg, H.A. Delineation of the hydroxyapatite-nucleating domains of bone sialoprotein. J. Biol. Chem. 2003 278:7949-55. PMID 12493752
  10. ^ Oldberg, A., Franzen, A., Heinegard, D. The primary structure of a cell-binding bone sialoprotein. J. Biol. Chem. 1988 263:19430-2 PMID 3198635
  11. ^ Tye, C.E., Hunter, G.K., Goldberg, H.A. Identification of the type I collagen-binding domain of bone sialoprotein and characterization of the mechanism of interaction. J. Biol. Chem. 2005 280:13487-92. PMID 15703183
  12. ^ Tye, C.E., Rattray, K.R., Warner, K.J., Gordon, J.A., Sodek, J., Hunter, G.K., Goldberg, H.A. Delineation of the hydroxyapatite-nucleating domains of bone sialoprotein. J. Biol. Chem. 2003 278:7949-55. PMID 12493752
  13. ^ Fisher, L.W., Whitson, S.W., Avioli, L.V., Termine, J.D. Matrix sialoprotein of developing bone. J. Biol. Chem. 1983 258:12723-7. PMID 6355090
  14. ^ Kinne, R.W., Fisher, L.W. Keratan sulfate proteoglycan in rabbit compact bone is bone sialoprotein II. J. Biol. Chem. 1987 262:10206-11. PMID 2956253
  15. ^ Ganss, B., Kim, R.H., Sodek, J. Bone sialoprotein. Crit. Rev. Oral. Bio. Med. 1999 10:79-98. PMID 10759428
  16. ^ Qin C et al. (2001) A comparative study of sialic acid-rich proteins in rat bone and dentin. Eur J Oral Sci 109:133-141. PMID 11347657
  17. ^ Huter GK & Goldberg HA (1994) Modulation of crystal formation by bone phosphoproteins: role of glutamic acid-rich sequences in the nucleation of hydroxyapatite by bone sialoprotein. Biochem J 302:175-179 PMID 7915111
 
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Bone_sialoprotein". A list of authors is available in Wikipedia.
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