6UJB

Integrin alpha-v beta-8 in complex with the Fabs C6D4 and 11D12v2

6UJB の概要

• エントリーDOI: 10.2210/pdb6ujb/pdb
• EMDBエントリー: 20794 20795 20796 20797 20798 20799 20800 20801 20802
• 分子名称: Integrin alpha-V, Integrin beta-8, C6D4 heavy chain Fab, ... (9 entities in total)
• 機能のキーワード: glycoprotein, adhesion, signaling, signaling protein-immune system complex, signaling protein/immune system
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 244675.14

構造登録者

Campbell, M.G.,Cormier, A.,Cheng, Y.,Nishimura, S.L. (登録日: 2019-10-02, 公開日: 2020-02-05, 最終更新日: 2024-11-06)

主引用文献

Campbell, M.G.,Cormier, A.,Ito, S.,Seed, R.I.,Bondesson, A.J.,Lou, J.,Marks, J.D.,Baron, J.L.,Cheng, Y.,Nishimura, S.L.
Cryo-EM Reveals Integrin-Mediated TGF-beta Activation without Release from Latent TGF-beta.
Cell, 180:490-, 2020

PubMed Abstract: Integrin αvβ8 binds with exquisite specificity to latent transforming growth factor-β (L-TGF-β). This binding is essential for activating L-TGF-β presented by a variety of cell types. Inhibiting αvβ8-mediated TGF-β activation blocks immunosuppressive regulatory T cell differentiation, which is a potential therapeutic strategy in cancer. Using cryo-electron microscopy, structure-guided mutagenesis, and cell-based assays, we reveal the binding interactions between the entire αvβ8 ectodomain and its intact natural ligand, L-TGF-β, as well as two different inhibitory antibody fragments to understand the structural underpinnings of αvβ8 binding specificity and TGF-β activation. Our studies reveal a mechanism of TGF-β activation where mature TGF-β signals within the confines of L-TGF-β and the release and diffusion of TGF-β are not required. The structural details of this mechanism provide a rational basis for therapeutic strategies to inhibit αvβ8-mediated L-TGF-β activation.

PubMed: 31955848
DOI: 10.1016/j.cell.2019.12.030

実験手法

ELECTRON MICROSCOPY (3.51 Å)