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- Title
Structural and functional insights into lipid-bound nerve growth factors.
- Authors
Qiong Tong; Feng Wang; Hong-Zhe Zhou; Han-Li Sun; Hui Song; Yu-Yan Shu; Yong Gong; Wen-Ting Zhang; Tan-xi Cai; Fu-Quan Yang; Jie Tang; Tao Jiang
- Abstract
Nerve growth factor (NGF) is a dimeric molecule that modulates the survival, proliferation, and differentiation of nervous cells and is also known to act on cells of the immune system and endocrine system. NGFs extracted from mouse submaxillary gland and cobra venom have different immunological behaviors, yet the underlying mechanism remains unclear. Here we report the crystal structure of the NGF purified from Chinese cobra Naja naja atra (cNGF), which unexpectedly reveals a 2-tailed lipid molecule that is embedded between the two protomers of the NGF homodimer. In addition, crystallographic analysis indicated that the purified mouse NGF(mNGF) is free from lipid but can bind lysophosphatidylserine (lyso- PS) in the same pocket as cNGF. Bioassays indicated that the binding of lipid molecules to cNGF and mNGF are essential for their mast cell activation activity and abates their p75NTR binding capacity. Taken together, these results suggest a new mechanism for the regulation of the function of NGF.
- Subjects
NERVE growth factor; MOLECULES; IMMUNE system; ENDOCRINE system; CYTOLOGICAL research; PHYSIOLOGICAL effects of venom
- Publication
FASEB Journal, 2012, Vol 26, Issue 9, p3811
- ISSN
0892-6638
- Publication type
Article
- DOI
10.1096/fj.12-207316