5URY

Crystal structure of Frizzled 5 CRD in complex with PAM

5URY の概要

• エントリーDOI: 10.2210/pdb5ury/pdb
• 分子名称: Frizzled-5, alpha-L-fucopyranose-(1-3)-[alpha-L-fucopyranose-(1-4)][alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, PALMITOLEIC ACID, ... (4 entities in total)
• 機能のキーワード: frizzled 5, crd, signaling protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 34706.66

構造登録者

Mukund, S.,Nile, A.H.,Stanger, K.,Hannoush, R.N.,Wang, W. (登録日: 2017-02-13, 公開日: 2017-05-10, 最終更新日: 2024-11-06)

主引用文献

Nile, A.H.,Mukund, S.,Stanger, K.,Wang, W.,Hannoush, R.N.
Unsaturated fatty acyl recognition by Frizzled receptors mediates dimerization upon Wnt ligand binding.
Proc. Natl. Acad. Sci. U.S.A., 114:4147-4152, 2017

PubMed Abstract: Frizzled (FZD) receptors mediate Wnt signaling in diverse processes ranging from bone growth to stem cell activity. Moreover, high FZD receptor expression at the cell surface contributes to overactive Wnt signaling in subsets of pancreatic, ovarian, gastric, and colorectal tumors. Despite the progress in biochemical understanding of Wnt-FZD receptor interactions, the molecular basis for recognition of Wnt -unsaturated fatty acyl groups by the cysteine-rich domain (CRD) of FZD receptors remains elusive. Here, we determined a crystal structure of human FZD7 CRD unexpectedly bound to a 24-carbon fatty acid. We also report a crystal structure of human FZD5 CRD bound to C16:1 -Δ9 unsaturated fatty acid. Both structures reveal a dimeric arrangement of the CRD. The lipid-binding groove exhibits flexibility and spans both monomers, adopting a U-shaped geometry that accommodates the fatty acid. Re-evaluation of the published mouse FZD8 CRD structure reveals that it also shares the same architecture as FZD5 and FZD7 CRDs. Our results define a common molecular mechanism for recognition of the -unsaturated fatty acyl group, a necessary posttranslational modification of Wnts, by multiple FZD receptors. The fatty acid bridges two CRD monomers, implying that Wnt binding mediates FZD receptor dimerization. Our data uncover possibilities for the arrangement of Wnt-FZD CRD complexes and shed structural insights that could aide in the identification of pharmacological strategies to modulate FZD receptor function.

PubMed: 28377511
DOI: 10.1073/pnas.1618293114

実験手法

X-RAY DIFFRACTION (2.098 Å)