title: Resonance assignment and secondary structure determination of full length human Dickkopf 4 (hDkk4), a secreted, disulphide-rich Wnt inhibitor protein.
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 (15)N, (13)C and (1)H 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.
authors.affiliation: Department of Biochemistry, Henry Wellcome Building, University of Leicester, Lancaster Road, Leicester, LE1 9HN, UK, amb68@le.ac.uk.
authors.forename: Alice M
authors.initials: AM
authors.lastname: Barkell
authors.forename: Gill
authors.initials: G
authors.lastname: Holdsworth
authors.forename: Lorna C
authors.initials: LC
authors.lastname: Waters
authors.forename: Vaclav
authors.initials: V
authors.lastname: Veverka
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Slocombe
authors.forename: Frederick W
authors.initials: FW
authors.lastname: Muskett
authors.forename: Alistair J
authors.initials: AJ
authors.lastname: Henry
authors.forename: Martyn K
authors.initials: MK
authors.lastname: Robinson
authors.forename: Mark D
authors.initials: MD
authors.lastname: Carr
mesh_terms: D004220:Disulfides; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000737:chemistry* / Q000378:metabolism*; D019906:Nuclear Magnetic Resonance, Biomolecular; D017433:Protein Structure, Secondary; D051153:Wnt Proteins / Q000037:antagonists & inhibitors*
chemical_list: C442333:DKK4 protein, human; D004220:Disulfides; D036341:Intercellular Signaling Peptides and Proteins; D051153:Wnt Proteins