Bone sialoprotein

Last updated
IBSP
Bone Sialoprotein Model.png
Identifiers
Aliases IBSP , BNSP, BSP, BSP-II, SP-II, integrin binding sialoprotein
External IDs OMIM: 147563 MGI: 96389 HomoloGene: 3644 GeneCards: IBSP
Orthologs
SpeciesHumanMouse
Entrez

3381

15891

Ensembl

ENSG00000029559

ENSMUSG00000029306

UniProt

P21815

Q61711

RefSeq (mRNA)

NM_004967

NM_008318

RefSeq (protein)

NP_004958

NP_032344

Location (UCSC) Chr 4: 87.8 – 87.81 Mb Chr 5: 104.45 – 104.46 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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. [5] BSP, a SIBLING protein, was originally isolated from bovine cortical bone as a 23-kDa glycopeptide with high sialic acid content. [6] [7]

Contents

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. [8]

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. [9] 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) [10] 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. [11] However, the majority of studies have demonstrated that BSP has no α-helical or β-sheet structure by 1D NMR [10] [12] and circular dichroism. [13] Analysis of native protein by electron microscopy confirm that the protein has an extended structure approximately 40 nm in length. [14] 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), [15] a hydroxyapatite-nucleating region of contiguous glutamic acid residues (rattus norvegicus residues 78–85, 155–164) [13] 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. [16] [17] 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. [18]

Function

The amount of BSP in bone and dentin is roughly equal, [19] 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. [20] 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. [21]

Related Research Articles

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Dentin sialophosphoprotein is a precursor protein for other proteins found in the teeth. It is produced by cells (odontoblasts) inside the teeth, and in smaller quantities by bone tissues. It is required for normal hardening (mineralisation) of teeth. During teeth development, it is broken down into three proteins such as dentin sialoprotein (DSP), dentin glycoprotein (DGP), and dentin phosphoprotein (DPP). These proteins become the major non-collagenous components of teeth. Their distribution in the collagen matrix of the forming dentin suggests these proteins play an important role in the regulation of mineral deposition. Additional evidence for this correlation is phenotypically manifested in patients with mutant forms of dentin sialophosphoprotein. Such patients suffer dental anomalies including type III dentinogenesis imperfecta.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000029559 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000029306 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ Fisher LW, McBride OW, Termine JD, Young MF (February 1990). "Human bone sialoprotein. Deduced protein sequence and chromosomal localization". J. Biol. Chem. 265 (4): 2347–51. doi: 10.1016/S0021-9258(19)39982-X . PMID   2404984.
  6. ↑ Williams PA, Peacocke AR (November 1965). "The physical properties of a glycoprotein from bovine cortical bone (bone sialoprotein)". Biochim. Biophys. Acta. 101 (3): 327–35. doi:10.1016/0926-6534(65)90011-4. PMID   5862222.
  7. ↑ Herring GM (February 1964). "Comparison of bovine bone sialoprotein and serum orosomucoid". Nature. 201 (4920): 709. Bibcode:1964Natur.201..709H. doi: 10.1038/201709a0 . PMID   14139700. S2CID   4210187.
  8. ↑ Kerr JM, Fisher LW, Termine JD, Wang MG, McBride OW, Young MF (August 1993). "The human bone sialoprotein gene (IBSP): genomic localization and characterization". Genomics. 17 (2): 408–15. doi:10.1006/geno.1993.1340. PMID   8406493.
  9. ↑ Fisher LW, Whitson SW, Avioli LV, Termine JD (October 1983). "Matrix sialoprotein of developing bone". J. Biol. Chem. 258 (20): 12723–7. doi: 10.1016/S0021-9258(17)44236-0 . PMID   6355090.
  10. 1 2 Stubbs JT, Mintz KP, Eanes ED, Torchia DA, Fisher LW (August 1997). "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. doi: 10.1359/jbmr.1997.12.8.1210 . PMID   9258751. S2CID   26407786.
  11. ↑ Shapiro HS, Chen J, Wrana JL, Zhang Q, Blum M, Sodek J (November 1993). "Characterization of porcine bone sialoprotein: primary structure and cellular expression". Matrix. 13 (6): 431–40. doi:10.1016/s0934-8832(11)80109-5. PMID   8309422.
  12. ↑ Fisher LW, Torchia DA, Fohr B, Young MF, Fedarko NS (January 2001). "Flexible structures of SIBLING proteins, bone sialoprotein, and osteopontin". Biochem. Biophys. Res. Commun. 280 (2): 460–5. doi:10.1006/bbrc.2000.4146. PMID   11162539.
  13. 1 2 Tye CE, Rattray KR, Warner KJ, Gordon JA, Sodek J, Hunter GK, Goldberg HA (March 2003). "Delineation of the hydroxyapatite-nucleating domains of bone sialoprotein". J. Biol. Chem. 278 (10): 7949–55. doi: 10.1074/jbc.M211915200 . PMID   12493752.
  14. ↑ Oldberg A, Franzén A, Heinegård D (December 1988). "The primary structure of a cell-binding bone sialoprotein". J. Biol. Chem. 263 (36): 19430–2. doi: 10.1016/S0021-9258(19)77651-0 . PMID   3198635.
  15. ↑ Tye CE, Hunter GK, Goldberg HA (April 2005). "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. doi: 10.1074/jbc.M408923200 . PMID   15703183.
  16. ↑ Kinne RW, Fisher LW (July 1987). "Keratan sulfate proteoglycan in rabbit compact bone is bone sialoprotein II". J. Biol. Chem. 262 (21): 10206–11. doi: 10.1016/S0021-9258(18)61099-3 . PMID   2956253.
  17. ↑ Ganss B, Kim RH, Sodek J (1999). "Bone sialoprotein". Crit. Rev. Oral Biol. Med. 10 (1): 79–98. doi: 10.1177/10454411990100010401 . PMID   10759428.
  18. ↑ Vincent K, Durrant MC (2013). "A structural and functional model for human bone sialoprotein" (PDF). J. Mol. Graph. Model. 39: 108–117. doi:10.1016/j.jmgm.2012.10.007. PMID   23261880.
  19. ↑ Qin C, Brunn JC, Jones J, George A, Ramachandran A, Gorski JP, Butler WT (April 2001). "A comparative study of sialic acid-rich proteins in rat bone and dentin". Eur. J. Oral Sci. 109 (2): 133–41. doi:10.1034/j.1600-0722.2001.00001.x. PMID   11347657.
  20. ↑ Hunter GK, Goldberg HA (August 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 ( Pt 1) (Pt 1): 175–9. doi:10.1042/bj3020175. PMC   1137206 . PMID   7915111.
  21. ↑ 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.

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