title: Critical role of Cys168 in noggin protein's biological function.
abstract: Previous studies have indicated that noggin exerts its neural inducing effect by binding and antagonizing bone morphogenetic protein 4 (BMP4). In order to further clarify the relationship between the structure and the function of noggin, and elucidate the possible mechanism responsible for noggin-BMP4 interaction, we generated three noggin mutants, C168S, C174S and C197S, by using a site-directed mutagenesis method. Ectopic expression of wild-type (WT) noggin, C174S or C197S, in Xenopus animal caps (ACs) by mRNA injection converted the explants (prospective ectoderm) into neural tissue, as indicated by the neural-like morphology and expression of the neural cell adhesion molecule (NCAM) in the ACs. In contrast, ACs expressing C168S suffered an epidermal fate similar to the control caps. Similarly, among the three mutants, only C168S lost the dorsalizing function. These studies highlight the critical role played by Cys168 in noggin's biological activities. It probably participates in the formation of an intermolecular disulfide bridge.
authors.affiliation: Cancer Research Institute, Central South University, Changsha, China.
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Liu
authors.forename: Xiang-Ling
authors.initials: XL
authors.lastname: Feng
authors.forename: Cai-Ping
authors.initials: CP
authors.lastname: Ren
authors.forename: Jian-Ling
authors.initials: JL
authors.lastname: Shi
authors.forename: Xu-Yu
authors.initials: XY
authors.lastname: Yang
authors.forename: Ming
authors.initials: M
authors.lastname: Zhao
authors.forename: Liang
authors.initials: L
authors.lastname: Zhou
authors.forename: Ke
authors.initials: K
authors.lastname: Lan
authors.forename: Kai-Tai
authors.initials: KT
authors.lastname: Yao
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D019521:Body Patterning / Q000502:physiology*; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins; D003545:Cysteine / Q000737:chemistry* / Q000378:metabolism*; D004627:Embryonic Induction / Q000502:physiology*; D006801:Humans; D008648:Mesoderm / Q000502:physiology*; D016297:Mutagenesis, Site-Directed; D009474:Neurons / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship; D014162:Transfection; D014982:Xenopus laevis; D000099176:Noggin Protein
chemical_list: D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D003545:Cysteine; D011994:Recombinant Proteins; D000099176:Noggin Protein