2YGN

WIF domain of human Wnt inhibitory factor 1 in complex with 1,2- dipalmitoylphosphatidylcholine

Summary for 2YGN

• Entry DOI: 10.2210/pdb2ygn/pdb
• Related: 2YGO 2YGP 2YGQ
• Descriptor: WNT INHIBITORY FACTOR 1, 1,2-DIACYL-SN-GLYCERO-3-PHOSHOCHOLINE, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• Functional Keywords: signaling protein, wnt signaling pathway, wnt antagonist, morphogen, cancer, glycosaminoglycan
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Secreted: Q9Y5W5
• Total number of polymer chains: 1
• Total formula weight: 18623.51

Authors

Malinauskas, T.,Aricescu, A.R.,Lu, W.,Siebold, C.,Jones, E.Y. (deposition date: 2011-04-19, release date: 2011-07-20, Last modification date: 2023-12-20)

Primary citation

Malinauskas, T.,Aricescu, A.R.,Lu, W.,Siebold, C.,Jones, E.Y.
Modular Mechanism of Wnt Signaling Inhibition by Wnt Inhibitory Factor 1
Nat.Struct.Mol.Biol., 18:886-, 2011

PubMed Abstract: Wnt morphogens control embryonic development and homeostasis in adult tissues. In vertebrates the N-terminal WIF domain (WIF-1(WD)) of Wnt inhibitory factor 1 (WIF-1) binds Wnt ligands. Our crystal structure of WIF-1(WD) reveals a previously unidentified binding site for phospholipid; two acyl chains extend deep into the domain, and the head group is exposed to the surface. Biophysical and cellular assays indicate that there is a WIF-1(WD) Wnt-binding surface proximal to the lipid head group but also implicate the five epidermal growth factor (EGF)-like domains (EGFs I-V) in Wnt binding. The six-domain WIF-1 crystal structure shows that EGFs I-V are wrapped back, interfacing with WIF-1(WD) at EGF III. EGFs II-V contain a heparan sulfate proteoglycan (HSPG)-binding site, consistent with conserved positively charged residues on EGF IV. This combination of HSPG- and Wnt-binding properties suggests a modular model for the localization of WIF-1 and for signal inhibition within morphogen gradients.

PubMed: 21743455
DOI: 10.1038/NSMB.2081

Experimental method

X-RAY DIFFRACTION (1.85 Å)