2g31
Human Nogo-A functional domain: nogo60
Structural highlights
FunctionRTN4_HUMAN Developmental neurite growth regulatory factor with a role as a negative regulator of axon-axon adhesion and growth, and as a facilitator of neurite branching. Regulates neurite fasciculation, branching and extension in the developing nervous system. Involved in down-regulation of growth, stabilization of wiring and restriction of plasticity in the adult CNS. Regulates the radial migration of cortical neurons via an RTN4R-LINGO1 containing receptor complex (By similarity). Isoform 2 reduces the anti-apoptotic activity of Bcl-xl and Bcl-2. This is likely consecutive to their change in subcellular location, from the mitochondria to the endoplasmic reticulum, after binding and sequestration. Isoform 2 and isoform 3 inhibit BACE1 activity and amyloid precursor protein processing.[1] [2] [3] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe 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. 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.,Li M, Liu J, Song J Protein Sci. 2006 Aug;15(8):1835-41. PMID:16877707[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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