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PDBsum entry 4eax
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Faseb J
26:3811-3821
(2012)
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PubMed id:
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Structural and functional insights into lipid-bound nerve growth factors.
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Q.Tong,
F.Wang,
H.Z.Zhou,
H.L.Sun,
H.Song,
Y.Y.Shu,
Y.Gong,
W.T.Zhang,
T.X.Cai,
F.Q.Yang,
J.Tang,
T.Jiang.
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ABSTRACT
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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 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.
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}
}
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