A cytoplasmic peptide of the neurotrophin receptor p75NTR: induction of apoptosis and NMR determined helical conformation.
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.
Hileman
M R
MR
Department of Chemistry, University of San Diego, CA 92110, USA.
Chapman
B S
BS
Rabizadeh
S
S
Krishnan
V V
VV
Bredesen
D
D
Assa-Munt
N
N
Plesniak
L A
LA
D017209:Apoptosis; D003497:Cyclic N-Oxides / Q000494:pharmacology; D006801:Humans; D050356:Lipid Metabolism; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000737:chemistry* / Q000378:metabolism; D013113:Spin Labels; D013329:Structure-Activity Relationship; D013696:Temperature; D014407:Tumor Cells, Cultured
D003497:Cyclic N-Oxides; D008823:Micelles; D010446:Peptide Fragments; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D013113:Spin Labels; C037404:12-doxylstearic acid