A cytoplasmic peptide of the neurotrophin receptor p75NTR: induction of apoptosis and NMR determined helical conformation

• Published in: FEBS letters 1997-09, Vol.415 (2), p.145-154
• Main Authors: Hileman, Matthew R., Chapman, Barbara S., Rabizadeh, S., Krishnan, V.V., Bredesen, Dale, Assa-Munt, Nuria, Plesniak, Leigh A.
• Format: Article
• Language: English
• Subjects: 14 amino acid fragment of NTR containing residues 368–381; 14 amino acid peptide containing NTR residues 367–380; 14 amino acid peptide containing residues 367–380 of human NTR sequence with lysine substitution at residue 373; Apoptosis; Chemical shift index; chemical shift indexing; CSI; Cyclic N-Oxides - pharmacology; dNN; dodecylphosphocholine-d38; DODPC; double quantum filtered correlated spectroscopy; DQF-COSY; FBS; fetal bovine serum; fusion peptide containing tat protein sequence and the lysine variant of NTR368; Humans; L373K; Lipid Metabolism; lysine variant of NTR368; Magnetic Resonance Spectroscopy; Micelle; Micelles; nerve growth factor receptor; NGFR; NOE cross peak between adjacent amide protons; NOESY; NTR; NTR367; NTR368; NTR368-L373K; nuclear Overhauser effect spectroscopy; p75 neurotrophin receptor; Peptide Fragments - chemical synthesis; Peptide Fragments - chemistry; Peptide Fragments - pharmacology; peptide fusion of tat protein with NTR368; Protein Conformation; Protein Structure, Secondary; Receptor, Nerve Growth Factor; Receptors, Nerve Growth Factor - chemistry; Receptors, Nerve Growth Factor - metabolism; rmsd; root mean square deviation; SDS; serum free medium; SFM; SH-SY; SH-SY-5Y human neuroblastoma cells; sodium dodecyl sulfate; Spin label; Spin Labels; Structure-Activity Relationship; tat-NTR368; tat-NTR368-L373K; Temperature; TNFR; TOCSY; total correlation spectroscopy; Tumor Cells, Cultured; tumor necrosis factor receptor
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/S0014-5793(97)01113-7

The neurotrophin receptor (NTR) and tumor necrosis factor receptor family of receptors regulate apoptotic cell death during development and in adult tissues [Beutler and van Huffel, Science 264 (1994) 667–668]. We have examined a fragment of p75NTR from the carboxyl terminus of the receptor and a variant form of this peptide via NMR techniques and in vitro assays for apoptotic activity. The wild type peptide induces apoptosis and adopts a helical conformation oriented parallel to the surface of lipid micelles, whereas the variant form adopts a non-helical conformation in the presence of lipid and shows no activity. These experiments suggest a link between structure and function of the two peptides.