4ec7
From Proteopedia
Cobra NGF in complex with lipid
Structural highlights
Function[NGFV_NAJAT] Nerve growth factor is important for the development and maintenance of the sympathetic and sensory nervous systems. It stimulates division and differentiation of sympathetic and embryonic sensory neurons as well as basal forebrain cholinergic neurons in the brain. Its relevance in the snake venom is not clear. However, it has been shown to inhibit metalloproteinase-dependent proteolysis of platelet glycoprotein Ib alpha, suggesting a metalloproteinase inhibition to prevent metalloprotease autodigestion and/or protection against prey proteases (By similarity). 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. See AlsoReferences
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Categories: Large Structures | Naja atra | Jiang T | Tong Q | Wang F
