Biomedical Engineering Reference
In-Depth Information
seen in proteins that do not undergo folding. The C-terminal domain consists of
only 11 amino acids, which are charged and hydrophilic. Although amelogenin
is an intrinsically disordered (natively unfolded) protein that does not have a
defined three-dimensional structure, it self-assembles and forms a
-sheet structure
at high concentrations [
16
]. Details concerning intrinsically disordered proteins
are discussed later in this chapter. Although the amelogenin molecule is highly
hydrophobic overall, due to the hydrophilic nature of the C-terminal region, it forms
an amphiphilic structure and self-assembles into nanospheres with a hydrodynamic
radius of 5-50 nm [
14
]. The nanospheres further aggregate and form a ribbon-like
structure on a micrometer scale [
17
]. It is of great interest to know what role this
high level of protein organization plays in the enamel formation process.
“
4.2.3
Role of SIBLING Protein Family in Extracellular
Matrices
The genes for the proteins involved in the crystallization of HAP are clustered on hu-
man chromosome 4 [
18
]. They include dentin sialophosphoprotein (DSPP), dentin
matrix protein 1 (DMP1), bovine sialoprotein (BSP), matrix extracellular phos-
phoglycoprotein (MEPE), osteopontin (OPN), enamelin (ENAM), ameloblastin
(AMBN), statherin (STATH), histatin (HYN), proline-rich proteins (PROL), and
caseins (CSN). DSPP, DMP1, BSP, MEPE, and OPN are expressed in bone
and dentin. These proteins belong to the small integrin-binding ligand N-linked
glycoprotein (SIBLING) family since they contain an integrin-binding motif (Arg-
Gly-Asp), are small, and are glycosylated [
19
]. Integrins are receptor proteins on
the cell surface that regulate intracellular signaling through the binding of ligands.
SIBLING proteins are believed to be involved in mineralization through their
interaction with calcium phosphates. They may also be involved in cell signaling
through interaction with integrins and other receptor proteins. These proteins may
play a role in cancer development [
20
].
Although their expression level is low, both ENAM and AMBN can be found
in enamel, together with amelogenin. STATH, HYN, and PROL are expressed in
saliva, while CSN is expressed in milk. The similarity of the exon and intron
organization and the repetitive sequences of the genes of these proteins imply that
they evolved from a common ancestor protein [
21
,
22
].
Among the SIBLING proteins, DMP1, BSP, and OPN can bind to collagen.
DSPP is proteolytically cleaved, resulting in DSP (dentin sialoprotein) and DPP
(dentin phosphoprotein or phosphophoryn) products. Among these proteins, DPP is
able to bind to collagen. Experiments on HAP crystal formation in the presence of
DMP1, BSP, OPN, and DPP showed that these proteins induce crystallization. They
most likely have the ability to bind to the collagen gap zone (See note above) and
form HAP crystals on collagen fibrils [
2
].
