5GRW

Crystal structure of homo-specific diabody

5GRW の概要

• エントリーDOI: 10.2210/pdb5grw/pdb
• 関連するPDBエントリー: 5GRU 5GRV 5GRX 5GRY 5GRZ 5GS0 5GS1 5GS2 5GS3
• 分子名称: homo-specific diabody protein (2 entities in total)
• 機能のキーワード: diabody, antibody fragment, immune system
• 由来する生物種: Homo sapiens
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 53801.45

構造登録者

Kim, J.H.,Song, D.H.,Youn, S.J.,Kim, J.W.,Cho, G.,Lee, H.,Lee, J.O. (登録日: 2016-08-12, 公開日: 2016-10-12, 最終更新日: 2024-10-09)

主引用文献

Kim, J.H.,Song, D.H.,Youn, S.J.,Kim, J.W.,Cho, G.,Kim, S.C.,Lee, H.,Jin, M.S.,Lee, J.O.
Crystal structure of mono- and bi-specific diabodies and reduction of their structural flexibility by introduction of disulfide bridges at the Fv interface.
Sci Rep, 6:34515-34515, 2016

PubMed Abstract: Building a sophisticated protein nano-assembly requires a method for linking protein components in a predictable and stable structure. Diabodies are engineered antibody fragments that are composed of two Fv domains connected by short peptide linkers. They are attractive candidates for mediators in assembling protein nano-structures because they can simultaneously bind to two different proteins and are rigid enough to be crystallized. However, comparison of previous crystal structures demonstrates that there is substantial structural diversity in the Fv interface region of diabodies and, therefore, reliable prediction of its structure is not trivial. Here, we present the crystal structures of ten mono- and bi-specific diabodies. We found that changing an arginine residue in the Fv interface to threonine greatly reduced the structural diversity of diabodies. We also found that one of the bispecific diabodies underwent an unexpected process of chain swapping yielding a non-functional monospecific diabody. In order to further reduce structural flexibility and prevent chain shuffling, we introduced disulfide bridges in the Fv interface regions. The disulfide-bridged diabodies have rigid and predictable structures and may have applications in crystallizing proteins, analyzing cryo-electron microscopic images and building protein nano-assemblies.

PubMed: 27682821
DOI: 10.1038/srep34515

実験手法

X-RAY DIFFRACTION (2.8 Å)