title: Hexapeptide fragment of carcinoembryonic antigen which acts as an agonist of heterogeneous ribonucleoprotein M.
abstract: Colorectal cancers with metastatic potential secrete the glycoprotein carcinoembryonic antigen (CEA). CEA has been implicated in colorectal cancer metastasis by inducing Kupffer cells to produce inflammatory cytokines which, in turn, make the hepatic micro-environment ideal for tumor cell implantation. CEA binds to the heterogeneous ribonucleoprotein M (hnRNP M) which acts as a cell surface receptor in Kupffer cells. The amino acid sequence in CEA, which binds the hnRNP M receptor, is Tyr-Pro-Glu-Leu-Pro-Lys. In this study, the structure of Ac-Tyr-Pro-Glu-Leu-Pro-Lys-NH₂ (YPELPK) was investigated using electronic circular dichroism, vibrational circular dichroism, and molecular dynamics simulations. The binding of the peptide to hnRNP M was also investigated using molecular docking calculations. The biological activity of YPELPK was studied using differentiated human THP-1 cells, which express hnRNP M on their surface and secrete IL-6 when stimulated by CEA. YPELPK forms a stable polyproline-II helix and stimulates IL-6 production of THP-1 cells at micromolar concentrations.
authors.affiliation: Departments of Biomedical Sciences, Creighton University, Omaha, NE 68178, USA.
authors.forename: Nicholas Y
authors.initials: NY
authors.lastname: Palermo
authors.forename: Peter
authors.initials: P
authors.lastname: Thomas
authors.forename: Richard F
authors.initials: RF
authors.lastname: Murphy
authors.forename: Sándor
authors.initials: S
authors.lastname: Lovas
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D002272:Carcinoembryonic Antigen / Q000737:chemistry* / Q000494:pharmacology; D002460:Cell Line; D034761:Heterogeneous-Nuclear Ribonucleoprotein Group M / Q000819:agonists* / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D006860:Hydrogen Bonding; D015850:Interleukin-6 / Q000096:biosynthesis; D056004:Molecular Dynamics Simulation; D010446:Peptide Fragments / Q000737:chemistry* / Q000494:pharmacology; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013499:Surface Properties; D013816:Thermodynamics
chemical_list: D002272:Carcinoembryonic Antigen; C440104:HNRNPM protein, human; D034761:Heterogeneous-Nuclear Ribonucleoprotein Group M; C508600:IL6 protein, human; D015850:Interleukin-6; D010446:Peptide Fragments