8BWL

Crystal structure of human Twisted gastrulation protein homolog 1 (TWSG1) in complex with human Growth Differentiation factor 5 (GDF5) and calcium

8BWL の概要

• エントリーDOI: 10.2210/pdb8bwl/pdb
• 分子名称: Growth/differentiation factor 5, Twisted gastrulation protein homolog 1, CALCIUM ION, ... (4 entities in total)
• 機能のキーワード: twisted gastrulation protein homolog 1 (twsg1), growth differentiation factor 5 (gdf5), transforming growth factor beta (tgf-beta) signalling pathway, extracellular protein., signaling protein
• 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: 42619.46

構造登録者

Malinauskas, T.,Rudolf, A.F.,Moore, G.,Eggington, H.,Belnoue-Davis, H.,El Omari, K.,Woolley, R.E.,Griffiths, S.C.,Duman, R.,Wagner, A.,Leedham, S.J.,Baldock, C.,Ashe, H.,Siebold, C. (登録日: 2022-12-06, 公開日: 2024-06-19, 最終更新日: 2024-11-20)

主引用文献

Malinauskas, T.,Moore, G.,Rudolf, A.F.,Eggington, H.,Belnoue-Davis, H.L.,El Omari, K.,Griffiths, S.C.,Woolley, R.E.,Duman, R.,Wagner, A.,Leedham, S.J.,Baldock, C.,Ashe, H.L.,Siebold, C.
Molecular mechanism of BMP signal control by Twisted gastrulation.
Nat Commun, 15:4976-4976, 2024

PubMed Abstract: Twisted gastrulation (TWSG1) is an evolutionarily conserved secreted glycoprotein which controls signaling by Bone Morphogenetic Proteins (BMPs). TWSG1 binds BMPs and their antagonist Chordin to control BMP signaling during embryonic development, kidney regeneration and cancer. We report crystal structures of TWSG1 alone and in complex with a BMP ligand, Growth Differentiation Factor 5. TWSG1 is composed of two distinct, disulfide-rich domains. The TWSG1 N-terminal domain occupies the BMP type 1 receptor binding site on BMPs, whereas the C-terminal domain binds to a Chordin family member. We show that TWSG1 inhibits BMP function in cellular signaling assays and mouse colon organoids. This inhibitory function is abolished in a TWSG1 mutant that cannot bind BMPs. The same mutation in the Drosophila TWSG1 ortholog Tsg fails to mediate BMP gradient formation required for dorsal-ventral axis patterning of the early embryo. Our studies reveal the evolutionarily conserved mechanism of BMP signaling inhibition by TWSG1.

PubMed: 38862520
DOI: 10.1038/s41467-024-49065-8

実験手法

X-RAY DIFFRACTION (1.96 Å)