6GFF

Structure of GARP (LRRC32) in complex with latent TGF-beta1 and MHG-8 Fab

6GFF の概要

• エントリーDOI: 10.2210/pdb6gff/pdb
• 分子名称: Transforming growth factor beta-1, Leucine-rich repeat-containing protein 32, MHG-8 Fab light chain, ... (8 entities in total)
• 機能のキーワード: garp, tgf-b1, activation, treg, immune system
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 14
• 化学式量合計: 398360.92

構造登録者

Merceron, R.,Lienart, S.,Vanderaa, C.,Colau, D.,Stockis, J.,Van Der Woning, B.,De Haard, H.,Saunders, M.,Coulie, P.G.,Savvides, S.N.,Lucas, S. (登録日: 2018-04-30, 公開日: 2018-11-07, 最終更新日: 2024-11-06)

主引用文献

Lienart, S.,Merceron, R.,Vanderaa, C.,Lambert, F.,Colau, D.,Stockis, J.,van der Woning, B.,De Haard, H.,Saunders, M.,Coulie, P.G.,Savvides, S.N.,Lucas, S.
Structural basis of latent TGF-beta 1 presentation and activation by GARP on human regulatory T cells.
Science, 362:952-956, 2018

PubMed Abstract: Transforming growth factor-β1 (TGF-β1) is one of very few cytokines produced in a latent form, requiring activation to exert any of its vastly diverse effects on development, immunity, and cancer. Regulatory T cells (T) suppress immune cells within close proximity by activating latent TGF-β1 presented by GARP (glycoprotein A repetitions predominant) to integrin αVβ8 on their surface. We solved the crystal structure of GARP:latent TGF-β1 bound to an antibody that stabilizes the complex and blocks release of active TGF-β1. This finding reveals how GARP exploits an unusual medley of interactions, including fold complementation by the amino terminus of TGF-β1, to chaperone and orient the cytokine for binding and activation by αVβ8. Thus, this work further elucidates the mechanism of antibody-mediated blockade of TGF-β1 activation and immunosuppression by T.

PubMed: 30361387
DOI: 10.1126/science.aau2909

実験手法

X-RAY DIFFRACTION (3.1 Å)