Document Type

Article

Publication Date

12-2018

Abstract

LDL, VLDL and other members of the low-density lipoparticles (LLPs) enter cells through a large family of receptors. The actual receptor ligand(s) in apolipoprotein B100, one of the main proteins of LLP, remain(s) unknown. The objective of this study was to identify true receptor ligand(s) in apo B100, a molecule of 4,563 residues. Apo B100 contains 33 analogues of Cardin-Weintraub Arginine/Lysine-based receptor ligand motifs and shares key Lysine motifs and sequence similarity with the LDL receptor-associated protein, RAP, MESD, and heat shock proteins. Eleven FITC-labeled synthetic peptides of 21 – 42 residues, with at least one ligand, were tested for binding and internalization using HeLa cells. All peptides bind but display different binding capacities and patterns. Peptides B0013, B0582, B2366, and B2932 mediate endocytosis and appear in distinct sites in the cytoplasm. B0708 and B3181 bind and remain on the cell surface as aggregates/clusters. Peptides B3119 (Site A) and B3347 (Site B), the putative ligands showed low binding and no cell entry capacity. Apo B100 regions in this study share similarities with related proteins of known function including chaperone proteins and Apo BEC Stimulating Protein, and not directly related proteins, e.g., the DNA-binding domain of Interferon Regulatory Factors, MSX2-Interacting Protein, and snake venom Zinc metalloproteinase-disintegrin-like proteins.

Comments

Original published version available at doi.org/10.1007/s10930-018-9792-8

Publication Title

The Protein Journal

DOI

10.1007/s10930-018-9792-8

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