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|Title:||Rational design, solution conformation and identification of functional residues of the soluble and structured Nogo-54, which mimics Nogo-66 in inhibiting the CNS neurite outgrowth|
|Authors:||Li, M. |
|Source:||Li, M., Liao, X., Qin, H., Song, J., Li, Y., Xiao, Z.-c., Liu, J. (2008). Rational design, solution conformation and identification of functional residues of the soluble and structured Nogo-54, which mimics Nogo-66 in inhibiting the CNS neurite outgrowth. Biochemical and Biophysical Research Communications 373 (4) : 498-503. ScholarBank@NUS Repository. https://doi.org/10.1016/j.bbrc.2008.06.052|
|Abstract:||The interaction between Nogo-66 and its receptor NgR represents a promising target for designing drugs to treat CNS axonal injury which often leads to permanent disability. Unfortunately, the isolated Nogo-66 is highly insoluble while its truncated form Nogo-40 is soluble but unstructured, thus retarding further characterization and application. Here, we rationally design another soluble form Nogo-54. CD and NMR characterization reveals that Nogo-54 is structured, and importantly, is able to mimic Nogo-66 in inhibiting neurite outgrowth. Strikingly, mutating its C-terminal four residues (Lys50, Glu51, Arg53, and Arg54) leads to a mutant Nogo-54m which has no dramatic structural change but whose inhibitory activity is completely abolished. This strongly suggests that the four charged residues contribute significantly to the inhibitory action of Nogo-66. Furthermore, our study also provides a soluble and structured mimic as well as a possible antagonist for Nogo-66 which may hold promising potential for various medical applications. © 2008 Elsevier Inc. All rights reserved.|
|Source Title:||Biochemical and Biophysical Research Communications|
|Appears in Collections:||Staff Publications|
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