Bone sialoprotein (BSP) is a component of

mineralized tissues Mineralized tissues are biological tissues that incorporate minerals into soft matrices. Typically these tissues form a protective shield or structural support. Bone, mollusc shells, deep sea sponge ''Euplectella'' species, radiolarians, diato ...

such as

bone A bone is a Stiffness, rigid Organ (biology), organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red blood cell, red and white blood cells, store minerals, provid ...

dentin Dentin () (American English) or dentine ( or ) (British English) ( la, substantia eburnea) is a calcified tissue of the body and, along with enamel, cementum, and pulp, is one of the four major components of teeth. It is usually covered by ena ...

cementum Cementum is a specialized calcified substance covering the root of a tooth. The cementum is the part of the periodontium that attaches the teeth to the alveolar bone by anchoring the periodontal ligament.Illustrated Dental Embryology, Histology, a ...

and calcified

cartilage Cartilage is a resilient and smooth type of connective tissue. In tetrapods, it covers and protects the ends of long bones at the joints as articular cartilage, and is a structural component of many body parts including the rib cage, the neck an ...

. 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 Sialic acids are a class of alpha-keto acid sugars with a nine-carbon backbone. The term "sialic acid" (from the Greek for saliva, - ''síalon'') was first introduced by Swedish biochemist Gunnar Blix in 1952. The most common member of this gr ...

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 (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

Structure

Native BSP has an apparent molecular weight of 60-80 kDa based on

SDS-PAGE SDS-PAGE (sodium dodecyl sulfate–polyacrylamide gel electrophoresis) is a Discontinuous electrophoresis, discontinuous electrophoretic system developed by Ulrich K. Laemmli which is commonly used as a method to separate proteins with molecular m ...

, 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 The alpha helix (α-helix) is a common motif in the secondary structure of proteins and is a right hand-helix conformation in which every backbone N−H group hydrogen bonds to the backbone C=O group of the amino acid located four residues e ...

and some

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

. 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 found in the body's various connective tissues. As the main component of connective tissue, it is the most abundant protein in mammals, making up from 25% to 35% of the whole ...

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

hydroxyapatite Hydroxyapatite, also called hydroxylapatite (HA), is a naturally occurring mineral form of calcium apatite with the formula Ca5(PO4)3(OH), but it is usually written Ca10(PO4)6(OH)2 to denote that the crystal unit cell comprises two entities. ...

-nucleating region of contiguous glutamic acid residues (''rattus norvegicus'' residues 78-85, 155-164) and a classical

integrin Integrins are transmembrane receptors that facilitate cell-cell and cell-extracellular matrix (ECM) adhesion. Upon ligand binding, integrins activate signal transduction pathways that mediate cellular signals such as regulation of the cell cycle, ...

-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 al ...

, tyrosine

sulfation Sulfation is the chemical reaction that entails the addition of SO3 group. In principle, many sulfations would involve reactions of sulfur trioxide (SO3). In practice, most sulfations are effected less directly. Regardless of the mechanism, the ...

and serine and threonine

phosphorylation In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology and could be driven by natural selection. Text was copied from this source, wh ...

, 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 OH−, F− and Cl− ions, respectively, in the crystal. The formula of the admixture of the three most common e ...

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