Structural and functional insights into lipid‐bound nerve growth factors

• DOI: 10.1096/fj.12-207316
• Publication Date: 2012-05-31T05:56:15Z
• 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
• Keywords: Models, Molecular; 0301 basic medicine; Sequence Homology, Amino Acid; Molecular Sequence Data; Crystallography, X-Ray; Histamine Release; Lipids; 3. Good health; Structure-Activity Relationship; 03 medical and health sciences; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Animals; Humans; Amino Acid Sequence; Elapidae; Mast Cells; Nerve Growth Factors

Nerve growth factor (NGF) is a dimeric molecule that modulates the survival, proliferation, and differentiation of nervous cells also known to act on immune system endocrine system. NGFs extracted from mouse submaxillary gland cobra venom have different immunological behaviors, yet underlying mechanism remains unclear. Here we report crystal structure NGF purified Chinese Naja naja atra (cNGF), which unexpectedly reveals 2-tailed lipid embedded between two protomers homodimer. In addition, crystallographic analysis indicated NGF(mNGF) free but can bind lysophosphatidylserine (lyso-PS) in same pocket as cNGF. Bioassays binding molecules cNGF mNGF are essential for their mast cell activation activity abates p75NTR capacity. Taken together, these results suggest new regulation function NGF.—Tong, Q., Wang, F., Zhou, H.-Z., Sun, H.-L., Song, H., Shu, Y.-Y., Gong, Y., Zhang, W.-T., Cai, T.-X., Yang, F.-Q., Tang, J., Jiang, T. Structural functional insights into lipid-bound nerve factors. FASEB J. 26, 3811–3821 (2012). www.fasebj.org