Structural Studies of Detergent-Solubilized and Vesicle-Reconstituted Low-Density Lipoprotein (LDL) Receptor†

The low-density lipoprotein (LDL) receptor plays a key role in maintaining circulating and cellular cholesterol homeostasis. The LDL receptor is a transmembrane glycoprotein whose biochemical and genetic properties have been extensively studied notably by Brown, Goldstein and colleagues [Brown, M. S., & Goldstein, J. L., (1986) Science 232, 34−47]. However, few if any structural studies of the LDL receptor have been reported, and details of its secondary and tertiary structure are lacking. In an attempt to determine the low-resolution structure of the LDL receptor, we have purified the receptor from bovine adrenal cortices using modifications of the method of Schneider et al. [Schneider, W. J., Goldstein, J. L., & Brown, M. S. (1985) Methods in Enzymol. 109, 405−417]. Using circular dichroism, the secondary structure of the detergent-solubilized bovine LDL receptor at 25 °C was shown to be 19% α-helix, 42% β-sheet, and 39% random coil. Interestingly, the detergent-solubilized receptor appeared to be quite...