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

Minfen Li, Yali Li, Xuanhao Liao, Jingxian Liu, Haina Qin, Zhi-Cheng Xiao, Jianxing Song

Research output: Contribution to journalArticleResearchpeer-review

5 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)498 - 503
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume373
Issue number4
DOIs
Publication statusPublished - 2008
Externally publishedYes

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