4eax | pdb_00004eax
Mouse NGF in complex with Lyso-PS
Structural highlights
Function[NGF_MOUSE] Nerve growth factor is important for the development and maintenance of the sympathetic and sensory nervous systems. Extracellular ligand for the NTRK1 and NGFR receptors, activates cellular signaling cascades through those receptor tyrosine kinase to regulate neuronal proliferation, differentiation and survival. Publication Abstract from PubMedNerve 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 p75(NTR) binding capacity. Taken together, these results suggest a new mechanism for the regulation of the function of 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 and functional insights into lipid-bound nerve growth factors. Structural and functional insights into lipid-bound nerve growth factors.,Tong Q, Wang F, Zhou HZ, Sun HL, Song H, Shu YY, Gong Y, Zhang WT, Cai TX, Yang FQ, Tang J, Jiang T FASEB J. 2012 Sep;26(9):3811-21. Epub 2012 May 30. PMID:22649032[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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