ApoE: the role of conserved residues in defining function.
The amino acid sequences of apolipoprotein E (apoE) from 63 different mammalian species have been downloaded from the protein database. The sequences were compared to human apoE4 to determine conserved and non-conserved sequences of amino acids. ApoE4 is the major risk factor for the development of late onset Alzheimer's disease while apoE3, which differs from apoE4 by a single amino acid change at position 112, poses little or no risk for the development of this disease. Thus, the two proteins appear to be structurally and functionally different. Seven highly conserved regions, representing approximately 47 amino acids (of 299) have been found. These regions are distributed throughout the protein and reflect ligand binding sites as well as regions proposed to be involved in the propagation of the cysteine-arginine change at position 112 to distant regions of the protein in the N- and C-terminal domains. Highly non-conserved regions are at the N- and C-terminal ends of the apoE protein.
Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, Missouri, 63110.
Carl
C
Frieden
D000544:Alzheimer Disease / Q000378:metabolism; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000925:Anticoagulants / Q000378:metabolism; D053318:Apolipoprotein E3 / Q000737:chemistry* / Q000378:metabolism; D053327:Apolipoprotein E4 / Q000737:chemistry* / Q000378:metabolism; D001057:Apolipoproteins E / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D017124:Conserved Sequence; D006493:Heparin / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011973:Receptors, LDL / Q000378:metabolism
D016229:Amyloid beta-Peptides; D000925:Anticoagulants; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D011973:Receptors, LDL; D006493:Heparin
Aβ binding; LDL receptor binding; allosteric pathway; amino acid sequences; heparin binding; lipoprotein binding