4F0A

Crystal structure of XWnt8 in complex with the cysteine-rich domain of Frizzled 8

4F0A の概要

• エントリーDOI: 10.2210/pdb4f0a/pdb
• 関連するPDBエントリー: 1IJY
• 分子名称: Frizzled-8, Protein Wnt-8, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
• 機能のキーワード: wnt signaling, ligand-receptor complex, wnt, frizzled, fatty acid acylation, glycosylation, signaling protein
• 由来する生物種: Mus musculus (mouse); 詳細
• 細胞内の位置: Membrane; Multi-pass membrane protein: Q61091; Secreted, extracellular space, extracellular matrix: P28026
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 52603.69

構造登録者

Janda, C.Y.,Waghray, D.,Levin, A.M.,Thomas, C.,Garcia, K.C. (登録日: 2012-05-03, 公開日: 2012-06-13, 最終更新日: 2024-11-27)

主引用文献

Janda, C.Y.,Waghray, D.,Levin, A.M.,Thomas, C.,Garcia, K.C.
Structural basis of Wnt recognition by Frizzled.
Science, 337:59-64, 2012

PubMed Abstract: Wnts are lipid-modified morphogens that play critical roles in development principally through engagement of Frizzled receptors. The 3.25 angstrom structure of Xenopus Wnt8 (XWnt8) in complex with mouse Frizzled-8 (Fz8) cysteine-rich domain (CRD) reveals an unusual two-domain Wnt structure, not obviously related to known protein folds, resembling a "hand" with "thumb" and "index" fingers extended to grasp the Fz8-CRD at two distinct binding sites. One site is dominated by a palmitoleic acid lipid group projecting from serine 187 at the tip of Wnt's thumb into a deep groove in the Fz8-CRD. In the second binding site, the conserved tip of Wnt's "index finger" forms hydrophobic amino acid contacts with a depression on the opposite side of the Fz8-CRD. The conservation of amino acids in both interfaces appears to facilitate ligand-receptor cross-reactivity, which has important implications for understanding Wnt's functional pleiotropy and for developing Wnt-based drugs for cancer and regenerative medicine.

PubMed: 22653731
DOI: 10.1126/science.1222879

実験手法

X-RAY DIFFRACTION (3.25 Å)