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Nogo goes in the pure water: Solution structure of Nogo‐60 and design of the structured and buffer‐soluble Nogo‐54 for enhancing CNS regeneration
Author(s) -
Li Minfen,
Liu Jingxian,
Song Jianxing
Publication year - 2006
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1110/ps.062306906
Subject(s) - buffer (optical fiber) , regeneration (biology) , chemistry , microbiology and biotechnology , biophysics , computer science , biology , telecommunications
The inability to determine the structure of the buffer‐insoluble Nogo extracellular domain retarded further design of Nogo receptor (NgR) antagonists to treat CNS axonal injuries. Very surprisingly, we recently discovered that Nogo‐60 was soluble and structured in salt‐free water, thus allowing the determination of the first Nogo structure by heteronuclear NMR spectroscopy. Nogo‐60 adopts an unusual helical structure with the N‐ and C‐terminal helices connected by a long middle helix. While the N‐helix has no contact with the rest of the molecule, the C‐helix flips back to pack against the 20‐residue middle helix. This packing appears to trigger the formation of the stable Nogo‐60 structure because Nogo‐40 with the last helix truncated is unstructured. The Nogo‐60 structure offered us rationales for further design of the structured and buffer‐soluble Nogo‐54, which may be used as a novel NgR antagonist. Furthermore, our discovery may imply a general solution to solubilizing a category of buffer‐insoluble proteins for urgent structural investigations.