Alpha-fetoprotein structure and function: relevance to isoforms, epitopes, and conformational variants.
Mammalian alpha-fetoprotein (AFP) is classified as a member of the albuminoid gene superfamily consisting of albumin, AFP, vitamin D (Gc) protein, and alpha-albumin. Molecular variants of AFP have long been reported in the biomedical literature. Early studies identified isoelectric pH isoforms and lectin-binding variants of AFP, which differed in their physicochemical properties, but not in amino acid composition. Genetic variants of AFP, differing in mRNA kilobase length, were later extensively described in rodent models during fetal/perinatal stages, carcinogenesis, and organ regeneration. With the advent of monoclonal antibodies in the early 1980s, multiple antigenic epitopes on native AFP were detected and categorized, culminating in the identification of six to seven major epitopes. During this period, various AFP-binding proteins and receptors were reported to inhibit certain AFP immunoreactions. Concomittantly, human and rodent AFP were cloned and the amino acid sequences of the translated proteins were divulged. Once the amino acid composition of the AFP molecule was known, enzymatic fragments could be identified and synthetic peptide segments synthesized. Following discovery of the molten globule form in 1981, the existence of transitory, intermediate forms of AFP were acknowledged and their physiological significance was realized. In the present review, the various isoforms and variants of AFP are discussed in light of their potential biological relevance.
Mizejewski
G J
GJ
Division of Molecular Medicine, Wadsworth Center, New York State Department of Health, Albany 12201, USA. mizejewski@wadsworth.org
D000595:Amino Acid Sequence; D000818:Animals; D000940:Antigenic Variation; D002241:Carbohydrates / Q000737:chemistry; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D018604:Epitope Mapping; D000939:Epitopes / Q000737:chemistry; D005260:Female; D005786:Gene Expression Regulation; D030342:Genetic Diseases, Inborn / Q000235:genetics; D014644:Genetic Variation; D006133:Growth Substances / Q000502:physiology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007108:Immune Tolerance; D008431:Maternal-Fetal Exchange; D018832:Molecular Chaperones / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D008969:Molecular Sequence Data; D005810:Multigene Family; D009369:Neoplasms / Q000188:drug therapy / Q000517:prevention & control; D010446:Peptide Fragments / Q000737:chemistry; D011247:Pregnancy; D011487:Protein Conformation; D020033:Protein Isoforms / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D000509:alpha-Fetoproteins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*
D002241:Carbohydrates; D015815:Cell Adhesion Molecules; D000939:Epitopes; D006133:Growth Substances; D018832:Molecular Chaperones; D010446:Peptide Fragments; D020033:Protein Isoforms; D000509:alpha-Fetoproteins