Serotonin binding sites. I. Structures of sites on myelin basic protein, LHRH, MSH, ACTH, interferon, serum albumin, ovalbumin and red pigment concentrating hormone.

We report the results of nuclear magnetic resonance spectroscopy studies of combinations of serotonin (5-hydroxytryptamine) with the tryptophan peptide sequence and similar peptides from myelin basic protein. The binding site appears to consist of the sequence Arg Phe Ser Trp. Similar serotonin binding sites were found to exist on LHRH (Tyr Ser Trp) and MSH-ACTH tetrapeptide (Phe Arg Trp). These binding sites are specific to serotonin as is demonstrated by lack of binding by dopamine, histamine, acetylcholine and a dozen other pharmacologically active amines and indoles. Drugs known to affect serotonin levels, e.g., fenfluramine and L-DOPA, bind weakly to these sites. Structural and functional similarities between the tryptophan peptide, LHRH, and MSH-ACTH with an ACTH-like peptide of human leukocyte interferon, with human and bovine serum albumin, hen ovalbumin, and with red pigment concentrating hormone suggest that the latter peptides may also contain similar serotonin binding sites. The elucidation of serotonin binding sites on these peptides and proteins has implications for understanding various aspects of cancer, autoimmunity, neurological disease, and peptide hormone control.