beta 2-Glycoprotein I. Molecular properties of an unusual apolipoprotein, apolipoprotein H

beta 2-Glycoprotein I (beta 2GI) has recently been identified as a component of circulating plasma lipoproteins. The metabolic role of this apolipoprotein is not known with certainty; it has been reported that beta 2GI has a high affinity for triglyceride-rich particles, causing their selective precipitation by detergents, and activates lipoprotein lipase in the in vitro hydrolysis of artificial lipid emulsions. In the present report, we have evaluated the secondary, tertiary, and quaternary structure of lipid-free beta 2GI. The weight average molecular weight of beta 2GI, as determined by sedimentation equilibrium measurements, was 43,000 in the presence and absence of denaturing agents. Thus, in contrast to other apolipoproteins, apolipoprotein H (apo-H) does not self-associate in aqueous solution. The circular dichroic spectra of apo-H is unusual in that there are no strong negative bands in the far-ultraviolet region of the spectrum; there is a weak positive maximum at 235 nm and a relatively weak negative maximum at 205 nm. Treatment with guanidinium chloride results in a loss of the positive band with only minor changes in the intensity of the band at 205 nm. Apolipoproteins A-I, A-II, C-I, and E, in contrast, have a secondary structure that contains a high percentage of residues in an alpha-helical configuration and undergo major changes in structure at low concentrations of guanidinium chloride. Highly flexible proteins, such as apolipoproteins A-I, A-II, and C-I, absorb rapidly and reversibly to air-water interfaces, whereas more rigid proteins, such as the classical globular proteins, interact with the interface more slowly and irreversibly. This difference is due to the loosely folded tertiary structure of apolipoproteins and the ease with which they can change structure to accommodate a given environment. The surface activity of beta 2GI at neutral pH resembles that of typical globular proteins. Treatment with acid or base, although causing only minor changes in the circular dichroic spectra, resulted in major increases in the rate of absorption to an air-water interface; under these conditions the rates of absorption were similar to that found for apolipoprotein A-I. These results are consistent with a more flexible structure for beta 2GI in acid or base that resembles other loosely folded apolipoproteins. beta 2GI associates with plasma lipoproteins and satisfies all of the criteria to be classified as an apolipoprotein. The secondary, tertiary, and quaternary structure of beta 2GI is, however, quite different from that of other well characterized apolipoproteins. This difference in structure would be expected to affect protein-lipid interactions; the relationship between apo-H and other apolipoproteins may be similar to that proposed for integral versus peripheral membrane proteins.