Three-Dimensional Structure of the LDL Receptor-Binding Domain of Human Apolipoprotein E

作者：Charles B. Wilson, Mark R. Wardell, Karl Heinrich Weisgraber, Robert W. Mahley, David A. Agard · 发表于：Science · 年份：1991 · DOI：10.1126/science.2063194 · 被引用次数：680 · 研究领域：Lipoproteins and Cardiovascular Health、Computational Drug Discovery Methods、Protein Structure and Dynamics

Human apolipoprotein E, a blood plasma protein, mediates the transport and uptake of cholesterol and lipid by way of its high affinity interaction with different cellular receptors, including the low-density lipoprotein (LDL) receptor. The three-dimensional structure of the LDL receptor-binding domain of apoE has been determined at 2.5 angstrom resolution by x-ray crystallography. The protein forms an unusually elongated (65 angstroms) four-helix bundle, with the helices apparently stabilized by a tightly packed hydrophobic core that includes leucine zipper-type interactions and by numerous salt bridges on the mostly charged surface. Basic amino acids important for LDL receptor binding are clustered into a surface patch on one long helix. This structure provides the basis for understanding the behavior of naturally occurring mutants that can lead to atherosclerosis.