8G4K

Complex of TbRII mini protein binder bound to the TbRII ECD

8G4K の概要

• エントリーDOI: 10.2210/pdb8g4k/pdb
• 分子名称: 5HCS_TGFBR2_1, TGF-beta receptor type-2, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: tbrii, tgf-b type ii receptor, computationally designed mini protein binder, mpb, signaling protein
• 由来する生物種: synthetic construct; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 24360.07

構造登録者

Schwartze, T.S.,Hinck, A.P. (登録日: 2023-02-09, 公開日: 2024-08-14, 最終更新日: 2025-09-03)

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.C.,Hinck, A.P.,Baker, D.
Design of high-affinity binders to immune modulating receptors for cancer immunotherapy.
Nat Commun, 16:2001-2001, 2025

PubMed Abstract: Immune receptors have emerged as critical therapeutic targets for cancer immunotherapy. Designed protein binders can have high affinity, modularity, and stability and hence could be attractive components of protein therapeutics directed against these receptors, but traditional Rosetta based protein binder methods using small globular scaffolds have difficulty achieving high affinity on convex targets. Here we describe the development of helical concave scaffolds tailored to the convex target sites typically involved in immune receptor interactions. We employed these scaffolds to design proteins that bind to TGFβRII, CTLA-4, and PD-L1, achieving low nanomolar to picomolar affinities and potent biological activity following experimental optimization. Co-crystal structures of the TGFβRII and CTLA-4 binders in complex with their respective receptors closely match the design models. These designs should have considerable utility for downstream therapeutic applications.

PubMed: 40011465
DOI: 10.1038/s41467-025-57192-z

実験手法

X-RAY DIFFRACTION (1.24 Å)