6NE2

Designed repeat protein in complex with Fz7

6NE2 の概要

• エントリーDOI: 10.2210/pdb6ne2/pdb
• 関連するPDBエントリー: 6NDZ
• 分子名称: Designed repeat protein binder, Frizzled-7, ACETATE ION, ... (7 entities in total)
• 機能のキーワード: frizzled, designed protein, biosynthetic protein, biosynthetic protein-signaling protein complex, biosynthetic protein/signaling protein
• 由来する生物種: Escherichia coli; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 36882.41

構造登録者

Miao, Y.,Jude, K.M.,Garcia, K.C. (登録日: 2018-12-15, 公開日: 2019-05-15, 最終更新日: 2024-11-20)

主引用文献

Dang, L.T.,Miao, Y.,Ha, A.,Yuki, K.,Park, K.,Janda, C.Y.,Jude, K.M.,Mohan, K.,Ha, N.,Vallon, M.,Yuan, J.,Vilches-Moure, J.G.,Kuo, C.J.,Garcia, K.C.,Baker, D.
Receptor subtype discrimination using extensive shape complementary designed interfaces.
Nat.Struct.Mol.Biol., 26:407-414, 2019

PubMed Abstract: To discriminate between closely related members of a protein family that differ at a limited number of spatially distant positions is a challenge for drug discovery. We describe a combined computational design and experimental selection approach for generating binders targeting functional sites with large, shape complementary interfaces to read out subtle sequence differences for subtype-specific antagonism. Repeat proteins are computationally docked against a functionally relevant region of the target protein surface that varies in the different subtypes, and the interface sequences are optimized for affinity and specificity first computationally and then experimentally. We used this approach to generate a series of human Frizzled (Fz) subtype-selective antagonists with extensive shape complementary interaction surfaces considerably larger than those of repeat proteins selected from random libraries. In vivo administration revealed that Wnt-dependent pericentral liver gene expression involves multiple Fz subtypes, while maintenance of the intestinal crypt stem cell compartment involves only a limited subset.

PubMed: 31086346
DOI: 10.1038/s41594-019-0224-z

実験手法

X-RAY DIFFRACTION (1.299 Å)