7MRZ

Structure of GDF11 bound to fused ActRIIB-ECD and Alk4-ECD with Anti-ActRIIB Fab fragment

7MRZ の概要

• エントリーDOI: 10.2210/pdb7mrz/pdb
• 分子名称: Growth/differentiation factor 11, Activin receptor type-2B,Activin receptor type-1B, Fab Heavy Chain, ... (6 entities in total)
• 機能のキーワード: growth factor, type i receptor, transforming growth factor beta, type ii receptor, ternary complex, gdf11, signaling protein, 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: 88371.92

構造登録者

Goebel, E.J.,Kattamuri, C.,Gipson, G.R.,Thompson, T.B. (登録日: 2021-05-10, 公開日: 2022-01-19, 最終更新日: 2024-10-30)

主引用文献

Goebel, E.J.,Kattamuri, C.,Gipson, G.R.,Krishnan, L.,Chavez, M.,Czepnik, M.,Maguire, M.C.,Grenha, R.,Hakansson, M.,Logan, D.T.,Grinberg, A.V.,Sako, D.,Castonguay, R.,Kumar, R.,Thompson, T.B.
Structures of activin ligand traps using natural sets of type I and type II TGF beta receptors.
Iscience, 25:103590-103590, 2022

PubMed Abstract: The 30+ unique ligands of the TGFβ family signal by forming complexes using different combinations of type I and type II receptors. Therapeutically, the extracellular domain of a single receptor fused to an Fc molecule can effectively neutralize subsets of ligands. Increased ligand specificity can be accomplished by using the extracellular domains of both the type I and type II receptor to mimic the naturally occurring signaling complex. Here, we report the structure of one "type II-type I-Fc" fusion, ActRIIB-Alk4-Fc, in complex with two TGFβ family ligands, ActA, and GDF11, providing a snapshot of this therapeutic platform. The study reveals that extensive contacts are formed by both receptors, replicating the ternary signaling complex, despite the inherent low affinity of Alk4. Our study shows that low-affinity type I interactions support altered ligand specificity and can be visualized at the molecular level using this platform.

PubMed: 35005539
DOI: 10.1016/j.isci.2021.103590

実験手法

X-RAY DIFFRACTION (3 Å)