Bone sialoprotein (BSP) is a component of mineralized tissues such as

bone A bone is a rigid organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red and white blood cells, store minerals, provide structure and support for the body, ...

dentin Dentin ( ) (American English) or dentine ( or ) (British English) () is a calcified tissue (biology), tissue of the body and, along with tooth enamel, enamel, cementum, and pulp (tooth), pulp, is one of the four major components of teeth. It i ...

, 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. BSP, a SIBLING protein, was originally isolated from bovine cortical bone as a 23-kDa glycopeptide with high sialic acid content. 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 In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

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. 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) 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 An alpha helix (or α-helix) is a sequence of amino acids in a protein that are twisted into a coil (a helix). The alpha helix is the most common structural arrangement in the Protein secondary structure, secondary structure of proteins. It is al ...

and some

β-sheet The beta sheet (β-sheet, also β-pleated sheet) is a common structural motif, motif of the regular protein secondary structure. Beta sheets consist of beta strands (β-strands) connected laterally by at least two or three backbone chain, backbon ...

. However, the majority of studies have demonstrated that BSP has no α-helical or β-sheet structure by 1D NMR and circular dichroism. Analysis of native protein by electron microscopy confirm that the protein has an extended structure approximately 40 nm in length. 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 Collagen () is the main structural protein in the extracellular matrix of the connective tissues of many animals. It is the most abundant protein in mammals, making up 25% to 35% of protein content. Amino acids are bound together to form a trip ...

-binding domain (''rattus norvegicus'' residues 36–57), a

hydroxyapatite Hydroxyapatite (International Mineralogical Association, IMA name: hydroxylapatite) (Hap, HAp, or HA) is a naturally occurring mineral form of calcium apatite with the Chemical formula, formula , often written to denote that the Crystal struc ...

-nucleating region of contiguous glutamic acid residues (''rattus norvegicus'' residues 78–85, 155–164) 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. These modifications, which include N- and O-linked

glycosylation Glycosylation is the reaction in which a carbohydrate (or ' glycan'), i.e. a glycosyl donor, is attached to a hydroxyl or other functional group of another molecule (a glycosyl acceptor) in order to form a glycoconjugate. In biology (but not ...

, tyrosine sulfation and serine and threonine

phosphorylation In biochemistry, phosphorylation is described as the "transfer of a phosphate group" from a donor to an acceptor. A common phosphorylating agent (phosphate donor) is ATP and a common family of acceptor are alcohols: : This equation can be writ ...

, 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.

Function

The amount of BSP in bone and dentin is roughly equal, 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 Apatite is a group of phosphate minerals, usually hydroxyapatite, fluorapatite and chlorapatite, with high concentrations of Hydroxide, OH−, Fluoride, F− and Chloride, Cl− ion, respectively, in the crystal. The formula of the admixture of ...

crystals. 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.

Structure

Function

References

External links

Further reading