Open AccessD1 cap region involved in the receptor recognition and neural cell survival activity of human ciliary neurotrophic factor.
Author(s) -
Makoto Inoue,
Chikao Nakayama,
Kaoru Kikuchi,
Tōru Kimura,
Yohko Ishige,
Akira Ito,
Masaharu Kanaoka,
Hiroshi Noguchi
Publication year - 1995
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.92.19.8579
Subject(s) - glycoprotein 130 , biology , receptor , ciliary neurotrophic factor , microbiology and biotechnology , mutant , neurotrophic factors , biochemistry , signal transduction , gene , stat3
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.