Structural studies of human Naked2: A biologically active intrinsically unstructured protein

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Abstract

Naked1 and 2 are two mammalian orthologs of Naked Cuticle, a canonical Wnt signaling antagonist in Drosophila. Naked2, but not Naked1, interacts with transforming growth factor-α (TGFα) and escorts TGFα-containing vesicles to the basolateral membrane of polarized epithelial cells. Full-length Naked2 is poorly soluble. Since most functional domains, including the Dishevelled binding region, EF-hand, vesicle recognition, and membrane targeting motifs, reside in the N-terminal half of the protein, we expressed and purified the first 217 residues of human Naked2 and performed a functional analysis of this fragment. Its circular dichroism (CD) and nuclear magnetic resonance (NMR) spectra showed no evidence of secondary and/or tertiary structure. The fragment did not bind calcium or zinc. These results indicate that the N-terminal half of Naked2 behaves as an intrinsically unstructured protein.

Original languageEnglish
Pages (from-to)911-915
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume350
Issue number4
DOIs
StatePublished - Dec 1 2006

Keywords

  • Circular dichroism
  • Intrinsically unstructured protein
  • Naked2
  • Nuclear magnetic resonance
  • Transforming growth factor-α

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