title: Nerve growth factor binding domain of the nerve growth factor receptor.
abstract: A structural analysis of the rat low-affinity nerve growth factor (NGF) receptor was undertaken to define the NGF binding domain. Mutant NGF receptor DNA constructs were expressed in mouse fibroblasts or COS cells, and the ability of the mutant receptor to bind NGF was assayed. In the first mutant, all but 16 amino acid residues of the intracellular domain of the receptor were removed. This receptor bound NGF with a Kd comparable to that of the wild-type receptor. A second mutant contained only the four cysteine-rich sequences from the extracellular portion of the protein. This mutant was expressed in COS cells and the resultant protein was a secreted soluble form of the receptor that was able to bind NGF. Two N-terminal deletions, in which either the first cysteine-rich sequence of the first and part of the second cysteine-rich sequences were removed, bound NGF. However, a mutant lacking all four cysteine-rich sequences was unable to bind NGF. These results show that the four cysteine-rich sequences of the NGF receptor contain the NGF binding domain.
authors.affiliation: Department of Neurobiology, Stanford University School of Medicine, CA 94305.
authors.forename: A A
authors.initials: AA
authors.lastname: Welcher
authors.forename: C M
authors.initials: CM
authors.lastname: Bitler
authors.forename: M J
authors.initials: MJ
authors.lastname: Radeke
authors.forename: E M
authors.initials: EM
authors.lastname: Shooter
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D002872:Chromosome Deletion; D007700:Kinetics; D007739:L Cells / Q000378:metabolism; D051379:Mice; D016254:Mutagenesis, Insertional; D009414:Nerve Growth Factors / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor; D015183:Restriction Mapping; D014162:Transfection
chemical_list: D009414:Nerve Growth Factors; D011956:Receptors, Cell Surface; D017475:Receptors, Nerve Growth Factor