Three-dimensional structure of the LDL receptor-binding domain of human apolipoprotein E.
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.
Wilson
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Howard Hughes Medical Institute, University of California, San Francisco 94143-0448.
Wardell
M R
MR
Weisgraber
K H
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Mahley
R W
RW
Agard
D A
DA
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
D001057:Apolipoproteins E; D011973:Receptors, LDL