3UYO

Crystal structure of monobody SH13/ABL1 SH2 domain complex

3UYO の概要

• エントリーDOI: 10.2210/pdb3uyo/pdb
• 関連するPDBエントリー: 3K2M 3NCS
• 分子名称: Tyrosine-protein kinase ABL1, Monobody SH13, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: engineered binding protein, antibody mimic, protein-protein complex, sh2 domain, atp-binding, phosphoprotein, tyrosine-protein kinase, signaling protein-protein binding complex, signaling protein/protein binding
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cytoplasm, cytoskeleton. Isoform IB: Nucleus membrane; Lipid-anchor: P00519
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 23872.24

構造登録者

Wojcik, J.B.,Koide, A.,Koide, S. (登録日: 2011-12-06, 公開日: 2011-12-28, 最終更新日: 2023-09-13)

主引用文献

Koide, A.,Wojcik, J.,Gilbreth, R.N.,Hoey, R.J.,Koide, S.
Teaching an old scaffold new tricks: monobodies constructed using alternative surfaces of the FN3 scaffold.
J.Mol.Biol., 415:393-405, 2012

PubMed Abstract: The fibronectin type III domain (FN3) has become one of the most widely used non-antibody scaffolds for generating new binding proteins. Because of its structural homology to the immunoglobulin domain, combinatorial libraries of FN3 designed to date have primarily focused on introducing amino acid diversity into three loops that are equivalent to antibody complementarity-determining regions. Here, we report an FN3 library that utilizes alternative positions for presenting amino acid diversity. We diversified positions on a β-sheet and surface loops that together form a concave surface. The new library produced binding proteins (termed "monobodies") to multiple target proteins, generally with similar efficacy as the original, loop-focused library. The crystal structure of a monobody generated from the new library in complex with its target, the Abl SH2 domain, revealed that a concave surface of the monobody, as intended in our design, bound to a convex surface of the target with the interface area being among the largest of published structures of monobody-target complexes. This mode of interaction differs from a common binding mode for single-domain antibodies and antibody mimics in which recognition loops recognize clefts in targets. Together, this work illustrates the utilization of different surfaces of a single immunoglobulin-like scaffold to generate binding proteins with distinct characteristics.

PubMed: 22198408
DOI: 10.1016/j.jmb.2011.12.019

実験手法

X-RAY DIFFRACTION (1.83 Å)