8GAB

Crystal structure of CTLA-4 in complex with a high affinity CTLA-4 binder

8GAB の概要

• エントリーDOI: 10.2210/pdb8gab/pdb
• 分子名称: CTLA-4 binder, Cytotoxic T-lymphocyte protein 4, POTASSIUM ION, ... (4 entities in total)
• 機能のキーワード: ctla-4, de novo protein design, high affinity binder, immune system, de novo protein-immune system complex, de novo protein/immune system
• 由来する生物種: synthetic construct; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 52647.08

構造登録者

Yang, W.,Almo, S.C.,Baker, D.,Ghosh, A. (登録日: 2023-02-22, 公開日: 2024-08-21, 最終更新日: 2024-10-23)

主引用文献

Yang, W.,Hicks, D.R.,Ghosh, A.,Schwartze, T.A.,Conventry, B.,Goreshnik, I.,Allen, A.,Halabiya, S.F.,Kim, C.J.,Hinck, C.S.,Lee, D.S.,Bera, A.K.,Li, Z.,Wang, Y.,Schlichthaerle, T.,Cao, L.,Huang, B.,Garrett, S.,Gerben, S.R.,Rettie, S.,Heine, P.,Murray, A.,Edman, N.,Carter, L.,Stewart, L.,Almo, S.,Hinck, A.P.,Baker, D.
Design of High Affinity Binders to Convex Protein Target Sites.
Biorxiv, 2024

PubMed Abstract: While there has been progress in the de novo design of small globular miniproteins (50-65 residues) to bind to primarily concave regions of a target protein surface, computational design of minibinders to convex binding sites remains an outstanding challenge due to low level of overall shape complementarity. Here, we describe a general approach to generate computationally designed proteins which bind to convex target sites that employ geometrically matching concave scaffolds. We used this approach to design proteins binding to TGFβRII, CTLA-4 and PD-L1 which following experimental optimization have low nanomolar to picomolar affinities and potent biological activity. Co-crystal structures of the TGFβRII and CTLA-4 binders in complex with the receptors are in close agreement with the design models. Our approach provides a general route to generating very high affinity binders to convex protein target sites.

PubMed: 38746206
DOI: 10.1101/2024.05.01.592114

実験手法

X-RAY DIFFRACTION (2.72 Å)