title: The carboxyl terminus of nerve growth factor is required for biological activity.
abstract: A series of mouse nerve growth factor (NGF) deletion mutants have been constructed using in vitro mutagenesis to define domains of the protein essential for its activity. Deletions of the amino or carboxyl termini of mature NGF or of an internal domain, which normally produces a surface-exposed reverse turn, have been analyzed. Mutants with deletions in the amino terminus or in the reverse turn retain significant biological activity, whereas, in contrast, a mutant NGF lacking the seven most carboxyl-terminal amino acids is appropriately synthesized but shows no measurable biological activity. These results suggests that the flexible carboxyl tail of NGF, and perhaps other neurotrophins, plays a crucial role in mediating receptor recognition and/or ligand binding.
authors.affiliation: Department of Neurobiology, Stanford University School of Medicine, California 94305-5401.
authors.forename: C C
authors.initials: CC
authors.lastname: Drinkwater
authors.forename: P A
authors.initials: PA
authors.lastname: Barker
authors.forename: U
authors.initials: U
authors.lastname: Suter
authors.forename: E M
authors.initials: EM
authors.lastname: Shooter
mesh_terms: D000818:Animals; D002455:Cell Division; D002460:Cell Line; D002522:Chlorocebus aethiops; D004252:DNA Mutational Analysis; D015870:Gene Expression / Q000187:drug effects; D016762:Genes, fos; D066298:In Vitro Techniques; D051379:Mice; D009414:Nerve Growth Factors / Q000737:chemistry*; D016716:PC12 Cells; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D020917:Receptor, trkA; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D011994:Recombinant Proteins; D017384:Sequence Deletion; D013329:Structure-Activity Relationship
chemical_list: D009414:Nerve Growth Factors; D011518:Proto-Oncogene Proteins; D017475:Receptors, Nerve Growth Factor; D011994:Recombinant Proteins; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA