Key subdomains in the C-terminal of cerebral dopamine neurotrophic factor regulate the protein secretion.
Cerebral dopamine neurotrophic factor (CDNF) is a novel evolutionary conserved neurotrophic factor (NTF) which can protect and repairs dopamine neurons in animal models of Parkinson's disease. The crystal structure of CDNF is dominated by eight α-helices and the 3-dimensional structure of CDNF consists of an N-terminal saposin-like domain and a C-terminal SAP-domain. In particular, the C-terminal domain contains two critical motifs, a CXXC motif and a putative ER retention signal sequences (KTEL) at the C-terminus, which indicate that CDNF may be involved in endoplasmic reticulum (ER) stress. In this study, we found that disrupting helix-7 in the C-terminal could significantly increase CDNF secretion. Moreover, we identified the 149aa-154aa is the key amino acids in helix-7. In all, these findings suggest that helix-7 in the C-terminal is important for CDNF secretion, which maybe potential affect CDNF function in ER stress.
Yuhuangding Hospital, Yantai, Shandong Province, China.
Hao
H
Liu
Weifang Medical College, Weifang, Shandong Province, China.
Chunling
C
Zhao
Yuhuangding Hospital, Yantai, Shandong Province, China.
Lin
L
Zhong
Yuhuangding Hospital, Yantai, Shandong Province, China.
Jie
J
Liu
Yuhuangding Hospital, Yantai, Shandong Province, China.
Shouxin
S
Zhang
Jining Medical College, Jining, Shandong Province, China.
Baohua
B
Cheng
Yuhuangding Hospital, Yantai, Shandong Province, China. Electronic address: leigong27@163.com.
Lei
L
Gong
D000818:Animals; D016297:Mutagenesis, Site-Directed; D009414:Nerve Growth Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000737:chemistry* / Q000378:metabolism*; D016716:PC12 Cells; D017434:Protein Structure, Tertiary; D051381:Rats; D013329:Structure-Activity Relationship
C577430:CDNF protein, rat; D009414:Nerve Growth Factors
CDNF; Endoplasmic reticulum stress; Neurotrophic factor; Secretion