Wnts grasp the WIF domain of Wnt Inhibitory Factor 1 at two distinct binding sites.
Wnts have a structure resembling a hand with "thumb" and "index" fingers that grasp the cysteine rich domains of Frizzled receptors at two distinct binding sites. In the present work we show that the WIF domain of Wnt Inhibitory Factor 1 is also bound by Wnts at two sites. Using C-terminal domains of Wnt5a and Wnt7a and arginine-scanning mutagenesis of the WIF domain we demonstrate that, whereas the N-terminal, lipid-modified "thumb" of Wnts interacts with the alkyl-binding site of the WIF domain, the C-terminal domain of Wnts (Wnt-CTD) binds to a surface on the opposite side of the WIF domain.
Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, P.O. Box 286, Budapest H-1519, Hungary. Electronic address: kerekes.krisztina@ttk.mta.hu.
Krisztina
K
Kerekes
Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, P.O. Box 286, Budapest H-1519, Hungary. Electronic address: banyai.laszlo@ttk.mta.hu.
László
L
Bányai
Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, P.O. Box 286, Budapest H-1519, Hungary. Electronic address: patthy.laszlo@ttk.mta.hu.
László
L
Patthy
D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D001120:Arginine / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites / Q000235:genetics; D006801:Humans; D007700:Kinetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D051153:Wnt Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000071818:Wnt-5a Protein
D048868:Adaptor Proteins, Signal Transducing; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; D012097:Repressor Proteins; C485569:WIF1 protein, human; C085389:WNT5A protein, human; C092778:WNT7A protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D001120:Arginine
Arginine-scanning mutagenesis; Cancer therapy; Homology modeling; Protein–protein interaction; Ryk receptor tyrosine kinase; WIF domain; Wnt; Wnt Inhibitory Factor 1