Critical role of Cys168 in noggin protein's biological function.
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.
Liu
Wei-Dong
WD
Cancer Research Institute, Central South University, Changsha, China.
Feng
Xiang-Ling
XL
Ren
Cai-Ping
CP
Shi
Jian-Ling
JL
Yang
Xu-Yu
XY
Zhao
Ming
M
Zhou
Liang
L
Lan
Ke
K
Yao
Kai-Tai
KT
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
D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D003545:Cysteine; D011994:Recombinant Proteins; D000099176:Noggin Protein