No abstract

Complete amino acid sequence of human plasma Zn-a2-glycoprotein and its homology to histocompatibility antigens ( ABSTRACTIn the present study the complete amino acid sequence of human plasma Zn-a2-glycoprotein was determined. This protein whose biological function is unknown consists of a single polypeptide chain of 276 amino acid residues including 8 tryptophan residues and has a pyroglutamyl residue at the amino terminus. The location of the two disuhlde bonds in the polypeptide chain was also established. The three glycans, whose structure was elucidated with the aid of 500 MHz 1H NMR spectroscopy, were sialylated Nbiantennas. The molecular weight calculated from the polypeptide and carbohydrate structure is 38,478, which is close to the reported value of -41,000 based on physicochemical measurements. The predicted secondary structure appeared to be comprised of 23% a-helix, 27% 13-sheet, and 22% 13-turns. The three N-glycans were found to be located in 1-turn regions. An unexpected finding was made by computer analysis of the sequence data; this revealed that Zn-a2-glycoprotein is closely related to antigens of the major histocompatibility complex in amino acid sequence and in domain structure. There was an unusually high degree of sequence homology with the a chains of class I histocompatibility antigens. Moreover, this plasma protein was shown to be a member of the immunoglobulin gene superfamily. Zn-a2-glycoprotein appears to be a truncated secretory major histocompatibility complex-related molecule, and it may have a role in the expression of the immune response.Zn-a2-glycoprotein (Zna2gp) (Mr =38,500) is one of several human plasma proteins of unknown function that have been highly purified and characterized in terms of chemical and physical chemical properties (1, 2). This protein was first isolated from fraction VI of the Cohn ethanol procedure, and its name derives from the fact that it was precipitated by addition of zinc ions (1). The purified protein appeared homogeneous on electrophoresis and on amino-terminal amino acid analysis, which revealed a blocked end group. However, polymorphism of Zna2gp was observed electrophoretically both for the native and the asialo form of the protein (3). The carbohydrate content was reported to be 18% and to consist of N-acetylneuraminic acid, galactose, mannose, fucose, and N-acetylglucosamine (1). The lack of N-acetylgalactosamine indicated the absence of O-glycans. Although the possible biological function of this protein is not known, it has been speculated that Zna2gp has a lectinlike determinant in common with nephritogenic urinary glycoproteins (2, 4).In this paper we describe the determination of the complete amino acid sequence of Zna2gp, including the location of the two disulfide bridges and the structure of the three carbohydrate units, and we discuss the possible secondary structure of this protein. An unexpected finding made by computer analysis of the sequence data is that Zna2gp is closely related to antigens of the major histocompatibility com...

No abstract

We previously isolated a family of bone-resorbing proteins from human cancer ascites fluid and established that the three purified bone-resorbing proteins were chemically and immunochemically related to each other and to alpha-2HS glycoprotein (alpha 2HS). After this finding we purified the normal human serum counterpart of these ascites proteins and studied its effects on bone resorption. The bone-resorbing properties of normal human serum alpha 2HS were examined in vitro over a wide dose range. This normal human serum glycoprotein had a biphasic effect on 45Ca2+ release from bone. More specifically, this protein stimulated bone resorption at the lower concentrations tested, with a maximum effect [treated over control ratio of 2.5 +/- 0.30 (+/- SE); P less than 0.01] at 40 micrograms/mL. In contrast, at doses above 40 micrograms/mL, a sharp decline in calcium mobilization occurred, with a return to baseline occurring above 80 micrograms/mL. These results suggest that serum alpha 2HS may participate in the regulation of bone metabolism in vivo.