title: Three-dimensional structure of the LDL receptor-binding domain of human apolipoprotein E.
abstract: 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.
authors.affiliation: Howard Hughes Medical Institute, University of California, San Francisco 94143-0448.
authors.forename: C
authors.initials: C
authors.lastname: Wilson
authors.forename: M R
authors.initials: MR
authors.lastname: Wardell
authors.forename: K H
authors.initials: KH
authors.lastname: Weisgraber
authors.forename: R W
authors.initials: RW
authors.lastname: Mahley
authors.forename: D A
authors.initials: DA
authors.lastname: Agard
mesh_terms: D000595:Amino Acid Sequence; D001057:Apolipoproteins E / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D003196:Computer Graphics; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011973:Receptors, LDL / Q000378:metabolism*; D014961:X-Ray Diffraction
chemical_list: D001057:Apolipoproteins E; D011973:Receptors, LDL