title: D1 cap region involved in the receptor recognition and neural cell survival activity of human ciliary neurotrophic factor.
abstract: Human ciliary neurotrophic factor (hCNTF), which promotes the cell survival and differentiation of motor and other neurons, is a protein belonging structurally to the alpha-helical cytokine family. hCNTF was subjected to three-dimensional structure modeling and site-directed mutagenesis to analyze its structure-function relationship. The replacement of Lys-155 with any other amino acid residue resulted in abolishment of neural cell survival activity, and some of the Glu-153 mutant proteins had 5- to 10-fold higher biological activity. The D1 cap region (around the boundary between the CD loop and helix D) of hCNTF, including both Glu-153 and Lys-155, was shown to play a key role in the biological activity of hCNTF as one of the putative receptor-recognition sites. In this article, the D1 cap region of the 4-helix-bundle proteins is proposed to be important in receptor recognition and biological activity common to alpha-helical cytokine proteins reactive with gp130, a component protein of the receptors.
authors.affiliation: Sumitomo Pharmaceuticals Research Center, Osaka, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Inoue
authors.forename: C
authors.initials: C
authors.lastname: Nakayama
authors.forename: K
authors.initials: K
authors.lastname: Kikuchi
authors.forename: T
authors.initials: T
authors.lastname: Kimura
authors.forename: Y
authors.initials: Y
authors.lastname: Ishige
authors.forename: A
authors.initials: A
authors.lastname: Ito
authors.forename: M
authors.initials: M
authors.lastname: Kanaoka
authors.forename: H
authors.initials: H
authors.lastname: Noguchi
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D001483:Base Sequence; D002470:Cell Survival / Q000187:drug effects; D020934:Ciliary Neurotrophic Factor; D016207:Cytokines / Q000235:genetics; D004252:DNA Mutational Analysis; D004305:Dose-Response Relationship, Drug; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009414:Nerve Growth Factors / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects*; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship
chemical_list: D000596:Amino Acids; D020934:Ciliary Neurotrophic Factor; D016207:Cytokines; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins