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

Biochem Biophys Res Commun. 2006 Dec 1;350(4):911-5. doi: 10.1016/j.bbrc.2006.09.121. Epub 2006 Oct 2.

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-alpha (TGFalpha) and escorts TGFalpha-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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Amino Acid Sequence
  • Calcium-Binding Proteins
  • Carrier Proteins / chemistry*
  • Carrier Proteins / ultrastructure*
  • Humans
  • Molecular Conformation
  • Protein Conformation
  • Solubility
  • Wnt Proteins / chemistry*

Substances

  • Adaptor Proteins, Signal Transducing
  • Calcium-Binding Proteins
  • Carrier Proteins
  • NKD2 protein, human
  • Wnt Proteins