Bone acidic glycoprotein-75 self-associates to form large macromolecular complexes.
Bone acidic glycoprotein-75 (BAG-75) displays a strong propensity to self-associate to form large fibrillar complexes above concentrations of 7 x 10(-8) M; acidic phosphoproteins osteopontin and bone sialoprotein do not form similar complexes. Although the majority of the data supporting this conclusion is derived from in vitro studies, the fact that similar sized complexes are observed in crude extracts of bone and calcified cartilage suggests that macromolecular BAG-75 complexes are also a component of mineralized matrices in vivo. An awareness of the existence of complexes in extracts from bone necessitates that these forms are accounted for in terms of the relative amounts of individual acidic phosphoproteins in bone matrix. We now estimate that the amount of BAG-75 in rat calvarial bone is equivalent to that of osteopontin. While BAG-75 is capable of binding up to 139 atoms of calcium/mole with an average affinity constant of 0.5-1.0 x 10(-3) M, millimolar concentrations of calcium are not required for self-association. Assuming macromolecular diffusion within osteoid is restricted, osteoblastic cells could control the extent of self-association through the rate at which BAG-75 is synthesized and secreted into the osteoid matrix. Based on these findings, we hypothesize that BAG-75 self-associates to form fibrillar complexes in vivo which function in a supportive mechanical role and/or as an electronegative ionic barrier. Electronegative BAG-75 barrier structures could play a role in concentrating phosphate ions within bone matrix, thus facilitating mineralization.
Gorski
J P
JP
Division of Molecular Biology and Biochemistry, School of Biological Sciences, University of Missouri-Kansas City 64110, USA. JPGORSKI@CCTR.UMKC.EDU
Kremer
E A
EA
Chen
Y
Y
D000818:Animals; D001842:Bone and Bones / Q000502:physiology; D002135:Calcium-Binding Proteins / Q000302:isolation & purification / Q000378:metabolism; D006023:Glycoproteins / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D006801:Humans; D046911:Macromolecular Substances; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry
D002135:Calcium-Binding Proteins; D006023:Glycoproteins; D046911:Macromolecular Substances; C076105:bone acidic glycoprotein-75, human; C512787:bone acidic glycoprotein-75, rat; D012967:Sodium Dodecyl Sulfate