Human glial cell-line-derived neurotrophic factor: a structure-function analysis.
Glial cell-line-derived neurotrophic factor (GDNF) is a protein known to enhance the survival of dopaminergic and motor neurons. It has been shown to have therapeutic potential in the treatment of Parkinson's disease and other neurodegenerative diseases. GDNF gene was modified by deletion and insertion mutagenesis using PCR methods. The various mutants were all highly expressed in Escherichia coli. The recombinant proteins were purified and their survival-promoting activities were determined by motor neurons. The result showed that the C-terminus was critical for structure stability of GDNF, and the alpha-helix, finger1 and finger2 regions were involved in receptor binding, while the N-terminus was not essential for the biological functions of GDNF.
Chen
Z Y
ZY
Department of Neurobiology, Second Military Medical University, 800 Xiangyin Road, Shanghai, 200433, China. chengzyk@online.sh.cn
He
Z Y
ZY
He
C
C
Lu
C L
CL
Wu
X F
XF
D000818:Animals; D001483:Base Sequence; D018360:Crystallography, X-Ray; D017931:DNA Primers / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006801:Humans; D008958:Models, Molecular; D009046:Motor Neurons / Q000187:drug effects; D016296:Mutagenesis; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D011487:Protein Conformation; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology; D013329:Structure-Activity Relationship
D017931:DNA Primers; C495039:GDNF protein, human; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D011994:Recombinant Proteins