Mapping of Structure-Function Peptide Sites on the Human Alpha-fetoprotein Amino Acid Sequence

Abstract

The structure of alpha-fetoprotein (AFP) is presen-ted in light of AFP membership and position in the albuminoid gene family in comparison to other gene family members. Ontogenetic AFP gene expression is reviewed considering AFP mRNA presence in various tissues at different times during development. The multiple molecular variant forms of AFP are discussed in relation to published reports of AFP binding proteins and cell surface receptors. The atlas further shows AFP as a protein consisting of multiple peptide-cassettes consisting of amino acid (AA) sequence stretches matched to peptide segments on prohormones and biological response modifier proteins. Such AFP peptide segments could potentially serve as delivery agents which could target vascular, neuroendocrine, or gastrointestinal cells. A discussion follows in which peptide epitopes, extracellular matrix proteins, serine proteases, extracellular matrix, and cellular adhesion AA identity sites on AFP are considered. The AFP molecule is also viewed as a carrier/ transport protein based on AA sequence comparison of various proteins that bind hydropho-bic ligands and heavy metals similar to AFP binding of such components. An analysis of trans-cription factors, tumor suppressors, and AA-rich motifs follows, interfaced with dimerization and nuclear localization sequence matches identified on the AFP molecule. Emphasis is further placed upon homeodomain and apoptosis AA sequence identi-ties given that AFP serves as a fetal, phasespecific protein throughout embryogenesis, histogenesis, and organogenesis. AFP AA sequences are further presented as peptide identification sites for Mapping of Structure-Function Peptide Sites on the Human Alpha-fetoprotein Amino Acid SequenceMizejewski GJ Atlas Genet Cytogenet Oncol Haematol. 2010; 14(2) 170 growth factors, receptors, cytoskeletal proteins, and chemo-kines. A closing discussion summarizes the multi-ple and varied motifs of peptide sequences matched to AAs on each of AFP's three domains. This study indicates that short peptide segments, in addition to full-length AFP, and domain and subdomain fragments of AFP, could be employed as functional agents to help unravel the complexity of biological roles ascribed to human AFP.

Review of the putative cell-surface receptors for alpha-fetoprotein: identification of a candidate receptor protein family

“…This diagram was reformated and redrawn from Refs. [1] and [2] Overall, the expression of AFP receptors by malignant cells appeared to reflect the presence of phenotypic properties specific to immature, incompletely differentiated cells.…”

“…Finally, does AFP associate with certain SR classes and subtypes? The physiological activities ascribed to AFP in the last several decades are many and varied [1,2]. Examples include the activities discussed below and those listed in Tables 5 and 7.…”

“…HAFP, a tumor-associated fetal protein, is classified as a member of a three-domain albuminoid protein family that currently consists of five members: albumin (ALB), vitamin-D binding protein (DBP), alpha-fetoprotein (AFP), alphaalbumin (α-ALB) [2], and the recently reported AFPrelated gene (ARG) protein [3]. Structurally, AFP contains 32 cysteine residues from disulfide bridges that result in folding of the polypeptide chain into layers of loops, producing a triplet domain, V-shaped molecule [2] (Fig. 1a, b).…”

The alpha-fetoprotein third domain receptor binding fragment: in search of scavenger and associated receptor targets

“…HAFP exhibits a triplicate domain structure configured by intramolecular loops dictated by disulfide bridging, resulting in a helical V-or U-shaped molecular structure ( Figure 1) [2,3]. This oncofetal protein is classified as a member of a three domain albuminoid protein family that currently consists of five members: albumin (ALB), vitamin-D binding protein (DBP), alpha-fetoprotein (AFP), alpha-albumin (alpha-ALB) and the AFP-related gene (ARG) protein [4].…”

Mechanism of Cancer Growth Suppression of Alpha-Fetoprotein Derived Growth Inhibitory Peptides (GIP): Comparison of GIP-34 versus GIP-8 (AFPep). Updates and Prospects

“…Human alpha-fetoprotein (HAFP) is tumor-associated fetal protein, termed an oncofetal protein, consisting of 609 amino acids (AAs) including a 19 amino acid (AA) signal sequence [1-3]. HAFP has been shown to be a growth enhancing factor in its circulating, compact-folded, native full length configuration in studies of both fetal and tumor cell growth and proliferation studies (Figure 1A) [4-6].…”