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Resonance assignment and secondary structure determination of full length human Dickkopf 4 (hDkk4), a secreted, disulphide-rich Wnt inhibitor protein

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Abstract

A number of proteins have been shown to modulate canonical Wnt signalling at the cell surface, including members of the Dickkopf (Dkk) family (Baron and Rawadi in J Endocrinol 148:2635–2643, 2007; Cruciat and Niehrs in Cold Spring Harb Perspect Biol 5:a015081, 2013). The Dkk family includes four secreted proteins (Dkk1-4), which are characterised by two highly conserved cysteine-rich regions corresponding to C24–C73 and C128–C201 in human Dkk4 (hDkk4). Here we report essentially complete backbone and comprehensive side chain 15N, 13C and 1H NMR assignments for full length mature hDkk4 (M1–L207) containing a short C-terminal hexa-histidine tag (E208–H222). Analysis of the backbone chemical shift data obtained indicates that there is a very limited amount of regular secondary structure, with only small stretches of β-strand identified in both cysteine-rich regions. The N-terminal region of hDkk4 (M1–G21) and the relatively long linker between the two cysteine-rich regions (E77–Q123) appear to be unstructured and relatively mobile.

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Acknowledgments

Dr. Alice Barkell was supported by the award of a Ph.D. studentship from the Biotechnology and Biological Sciences Research Council in partnership with UCB. This work was also supported by a collaborative research grant from UCB to Prof. Mark Carr.

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Correspondence to Alice M. Barkell.

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Barkell, A.M., Holdsworth, G., Waters, L.C. et al. Resonance assignment and secondary structure determination of full length human Dickkopf 4 (hDkk4), a secreted, disulphide-rich Wnt inhibitor protein. Biomol NMR Assign 9, 147–151 (2015). https://doi.org/10.1007/s12104-014-9562-2

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  • DOI: https://doi.org/10.1007/s12104-014-9562-2

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