Apolipoprotein E gene and protein

Posted in the Biology Forum

Since: May 12

Fremont, CA

#1 May 29, 2012
Taylor established the cDNA sequence of APOE, Breslow and Zannis first measured APOE isomer of the three alleles and gene on chromosome positioning. Of APOE gene is located on the 19th of the long arm of chromosome 13 band (19q1312), the gene is 317kb and contains four exons and three introns. From 5 'to 3' exon length of 44bp, 66bp, 193bp and 860 bp, intron length is 760bp, 1092bp and 582bp. CDNA 11163kb, APOE precursor protein of 317 amino acids, containing 18 amino acid signal peptide, mature APOE protein of 299 amino acids.

Human APOE and rodent nucleotide sequence of the APOE with high homology to the nucleotide sequence of the two signal peptide region has 81% homology, the amino acid sequence of the signal peptide region of 67% in the same endogenous.Com parison of human and rodent mRNA sequences found both with 75% homology to the amino acid sequence has 70% homology.
APOE gene has three alleles, ε2, ε3 and ApoE ε4, respectively, and the resulting six genotypes, namely, of APOE2 / 2, E3 / 3, E4 / 4 three homozygous and APOE2 / 3 three heterozygous E2 / 4, E3 / 4 type. ε3, APOE3 / 3 are the most common allele and genotype, the gene frequency of 77%, 8% ε2 gene frequency, the APOE ε4 gene frequency of 15%, but the APOE gene frequencies in different ethnic and geographicaland the distribution of phenotypes may be different, but no gender differences in Chinese and Japanese are very similar to the ε3 frequency higher than 80%, while Europe and the United States per capita below 80%, European ε4 allele frequency decreasing from north to south trends in the distribution. Asian low-ε4 frequency (419%- 1217%), compared to African and Papua Shakespeare and New Guinea ε4 frequency (about 30% and 3618%), perhaps this is the United States and Europe AD a high incidence of a potential factor.

APOE is composed of 299 amino acids containing 32 Arg and 12 of Lys, the arginine content of up to 11%, an arginine-rich basic protein synthesis after glycosylation modification, but the plasma mature APOE is de-sialylated. Rall is equal to the measure of a structure of the APOE protein in 1982, according to projections and determination of APOE in the medium, 62% α-helix, 9% β-sheet, 11% β-turn and 18% rules of the line group. APOE molecule thrombin hydrolysis that is, for the two major structural domains: the N - terminal region (1-191) for the 22kDa soluble globulin, this area is relatively stable, 136 to 158 of the fragment peptide receptor binding sites, rich in basic amino acids (lysine and arginine), also belong to the heparin-binding domain. X - ray crystallographic studies showed that this fragment is an anti-parallel four-helix bundle, the fold of the α-helix protein. C-terminal region (216 299) molecular weight of 10kDa, the spiral degree of high, unstable, and the lipoprotein-binding domain. These two domains twisted by the period of the district (165 - 215 peptide) is connected.

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