Modulation of crystal formation by bone phosphoproteins: role of glutamic acid-rich sequences in the nucleation of hydroxyapatite by bone sialoprotein.
Bone sialoprotein (BSP) is a bone-specific glycoprotein containing phosphoserine and sulphotyrosine residues and regions of contiguous glutamic acid residues. Recent studies in this laboratory have shown that BSP is capable of nucleating the bone mineral hydroxyapatite in a steady-state agarose gel system. We show here that chemical modification of carboxylate groups abolishes the nucleation activity of BSP, but enzymic dephosphorylation has no effect. Formation of hydroxyapatite is also induced by poly(L-glutamic acid) and poly(D-glutamic acid), but not by poly(L-aspartic acid) or poly(L-lysine). Calreticulin, a muscle protein with short sequences of contiguous glutamic acid residues, also lacks nucleation activity. These findings suggest that the nucleation of hydroxyapatite by BSP involves one or both of the glutamic acid-rich sequences. Based on these findings and others, we propose that polycarboxylate sequences represent a general site for growth-modulating interactions between proteins and biological crystals.
Hunter
G K
GK
Division of Oral Biology, Faculty of Dentistry, University of Western Ontario, London, Canada.
Goldberg
H A
HA
D000595:Amino Acid Sequence; D000818:Animals; D001842:Bone and Bones / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000494:pharmacology; D037282:Calreticulin; D002264:Carboxylic Acids / Q000378:metabolism; D003460:Crystallization; D017886:Durapatite / Q000378:metabolism*; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D058574:Integrin-Binding Sialoprotein; D008969:Molecular Sequence Data; D010455:Peptides / Q000494:pharmacology; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D012261:Ribonucleoproteins / Q000494:pharmacology; D012795:Sialoglycoproteins / Q000378:metabolism*; D013552:Swine
D002135:Calcium-Binding Proteins; D037282:Calreticulin; D002264:Carboxylic Acids; D005971:Glutamates; D058574:Integrin-Binding Sialoprotein; D010455:Peptides; D010750:Phosphoproteins; D012261:Ribonucleoproteins; D012795:Sialoglycoproteins; D018698:Glutamic Acid; D017886:Durapatite