2G31: Human Nogo-A functional domain: nogo60

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.
PDB ID: 2G31Download
MMDB ID: 40880
PDB Deposition Date: 2006/2/17
Updated in MMDB: 2007/10
Experimental Method:
solution nmr
Source Organism:
Similar Structures:
Molecular Components in 2G31
Label Count Molecule
Protein (1 molecule)
Reticulon-4(Gene symbol: RTN4)
Molecule annotation
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