2OBG

Crystal Structure of Monobody MBP-74/Maltose Binding Protein Fusion Complex

2OBG の概要

• エントリーDOI: 10.2210/pdb2obg/pdb
• 分子名称: Maltose Binding periplasmic Protein and Monobody MBP-74 Fusion protein (2 entities in total)
• 機能のキーワード: domain swapping, binding protein, antibody mimic, binary interface, de novo protein, protein binding
• 由来する生物種: Escherichia coli, synthetic construct (,)
• 細胞内の位置: Periplasm: P0AEX9
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 50543.74

構造登録者

Gilbreth, R.N.,Tereshko, V.,Koide, S. (登録日: 2006-12-19, 公開日: 2007-03-27, 最終更新日: 2023-12-27)

主引用文献

Koide, A.,Gilbreth, R.N.,Esaki, K.,Tereshko, V.,Koide, S.
High-affinity single-domain binding proteins with a binary-code interface.
Proc.Natl.Acad.Sci.Usa, 104:6632-6637, 2007

PubMed Abstract: High degrees of sequence and conformation complexity found in natural protein interaction interfaces are generally considered essential for achieving tight and specific interactions. However, it has been demonstrated that specific antibodies can be built by using an interface with a binary code consisting of only Tyr and Ser. This surprising result might be attributed to yet undefined properties of the antibody scaffold that uniquely enhance its capacity for target binding. In this work we tested the generality of the binary-code interface by engineering binding proteins based on a single-domain scaffold. We show that Tyr/Ser binary-code interfaces consisting of only 15-20 positions within a fibronectin type III domain (FN3; 95 residues) are capable of producing specific binding proteins (termed "monobodies") with a low-nanomolar K(d). A 2.35-A x-ray crystal structure of a monobody in complex with its target, maltose-binding protein, and mutation analysis revealed dominant contributions of Tyr residues to binding as well as striking molecular mimicry of a maltose-binding protein substrate, beta-cyclodextrin, by the Tyr/Ser binary interface. This work suggests that an interaction interface with low chemical diversity but with significant conformational diversity is generally sufficient for tight and specific molecular recognition, providing fundamental insights into factors governing protein-protein interactions.

PubMed: 17420456
DOI: 10.1073/pnas.0700149104

実験手法

X-RAY DIFFRACTION (2.35 Å)