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

Abstract

Recent studies have demonstrated that the carboxyterminal third domain of alpha-fetoprotein (AFP-CD) binds with various ligands and receptors. Reports within the last decade have established that AFP-CD contains a large fragment of amino acids that interact with several different receptor types. Using computer software specifically designed to identify protein-to-protein interaction at amino acid sequence docking sites, the computer searches identified several types of scavenger-associated receptors and their amino acid sequence locations on the AFP-CD polypeptide chain. The scavenger receptors (SRs) identified were CD36, CD163, Stabilin, SSC5D, SRB1 and SREC; the SR-associated receptors included the mannose, low-density lipoprotein receptors, the asialoglycoprotein receptor, and the receptor for advanced glycation endproducts (RAGE). Interestingly, some SR interaction sites were localized on the AFP-derived Growth Inhibitory Peptide (GIP) segment at amino acids #480-500. Following the detection studies, a structural subdomain analysis of both the receptor and the AFP-CD revealed the presence of epidermal growth factor (EGF) repeats, extracellular matrix-like protein regions, amino acid-rich motifs and dimerization subdomains. For the first time, it was reported that EGF-like sequence repeats were identified on each of the three domains of AFP. Thereafter, the localization of receptors on specific cell types were reviewed and their functions were discussed.

• Alpha-fetoprotein
• binding proteins
• fragments
• growth inhibitory peptide
• macrophages
• monocytes
• scavenger receptors
• third domain

Acknowledgements

The author wishes to thank Mr. Andrew Bentley (Wadsworth Center Photography and Medical Illustration Department) for his expertise in producing the figures and graphic art illustrations in the manuscript. Gratitude is also extended to Ms. Jennifer Wright and Ms. Tracy Godfrey for the typing and processing of this paper. Acknowledgment is also made to Serometrics Biotech, LLC, Syracuse, NY, for use of their proprietary software computer program.

Declaration of interest

There are no conflicts of interest involved.