Acidic phosphoproteins from bone matrix: a structural rationalization of their role in biomineralization.
Osteopontin, bone sialoprotein, and bone acidic glycoprotein-75 are three acidic phosphoproteins that are isolated from the mineralized phase of bone matrix, are synthesized by osteoblastic cells, and are generally restricted in their distribution to calcified tissues. Although each is a distinct gene product, these proteins share aspartic/glutamic acid contents of 30-36% and each contains multiple phosphoryl and sialyl groups. These properties, plus a strict relationship of acidic macromolecules with cell-controlled mineralization throughout nature, suggest functions in calcium binding and nucleation of calcium hydroxyapatite crystal formation. However, direct proof for such roles is still largely indirect in nature. The purpose of this review is to present two speculative hypotheses regarding acidic phosphoprotein function. The goal was to use new sequence information along with database comparisons to develop a structural rationalization of how these proteins may function in calcium handling by bone. For example, our analysis has identified a conserved polyacidic stretch in all three phosphoproteins which we propose mediates metal binding. Also, conserved motifs were identified that are analogous with those for casein kinase II phosphorylation sites and whose number correlates well with that of phosphoryl groups/protein. A two-state conformational model of calcium binding by bone matrix acidic phosphoproteins is described which incorporates these findings.
Gorski
J P
JP
Division of Molecular Biology and Biochemistry, School of Basic Life Sciences, University of Missouri-Kansas City 64110.
D000595:Amino Acid Sequence; D000818:Animals; D015519:Bone Density / Q000502:physiology; D001857:Bone Matrix / Q000737:chemistry* / Q000502:physiology*; D002113:Calcification, Physiologic / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000032:analysis* / Q000737:chemistry / Q000502:physiology*
D010750:Phosphoproteins