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 pho sphoserine sulphotyrosine residues and regions of contiguous glutamic acid residues. Recent studies in this laboratory have shown that BSP i s capable of nucleating the bone mineral hydroxyapatite in a steady-st ate agarose gel system. We show here that chemical modification of car boxylate groups abolishes the nucleation activity of BSP, but enzymic dephosphorylation has no effect. Formation of hydroxyapatite is also i nduced by poly(L-glutamic acid) and poly(D-glutamic acid), but not by poly(L-aspartic acid) or poly(L-lysine). Calreticulin, a muscle protei n with short sequences of contiguous glutamic acid residues, also lack s nucleation activity. These findings suggest that the nucleation of h ydroxyapatite by BSP involves one or both of the glutamic acid-rich se quences. Based on these findings and others, we propose that polycarbo xylate sequences represent a general site for growth-modulating intera ctions between proteins and biological crystals.