5AEJ

Crystal structure of human Gremlin-1

5AEJ の概要

• エントリーDOI: 10.2210/pdb5aej/pdb
• 分子名称: GREMLIN-1, SULFATE ION (3 entities in total)
• 機能のキーワード: signaling protein, signaling, gremlin, growth factors, inhibitor, cystine knot, extracellular signalling, dan family
• 由来する生物種: HOMO SAPIENS (HUMAN)
• 細胞内の位置: Secreted : O60565
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 70332.73

構造登録者

Kisonaite, M.,Hyvonen, M. (登録日: 2015-08-31, 公開日: 2016-04-13, 最終更新日: 2024-11-13)

主引用文献

Kisonaite, M.,Wang, X.,Hyvonen, M.
Structure of Gremlin-1 and Analysis of its Interaction with Bmp-2.
Biochem.J., 473:1593-, 2016

PubMed Abstract: Bone morphogenetic protein 2 (BMP-2) is a member of the transforming growth factor-β (TGF-β) signalling family and has a very broad biological role in development. Its signalling is regulated by many effectors: transmembrane proteins, membrane-attached proteins and soluble secreted antagonists such as Gremlin-1. Very little is known about the molecular mechanism by which Gremlin-1 and other DAN (differential screening-selected gene aberrative in neuroblastoma) family proteins inhibit BMP signalling. We analysed the interaction of Gremlin-1 with BMP-2 using a range of biophysical techniques, and used mutagenesis to map the binding site on BMP-2. We have also determined the crystal structure of Gremlin-1, revealing a similar conserved dimeric structure to that seen in other DAN family inhibitors. Measurements using biolayer interferometry (BLI) indicate that Gremlin-1 and BMP-2 can form larger complexes, beyond the expected 1:1 stoichiometry of dimers, forming oligomers that assemble in alternating fashion. These results suggest that inhibition of BMP-2 by Gremlin-1 occurs by a mechanism that is distinct from other known inhibitors such as Noggin and Chordin and we propose a novel model of BMP-2-Gremlin-1 interaction yet not seen among any BMP antagonists, and cannot rule out that several different oligomeric states could be found, depending on the concentration of the two proteins.

PubMed: 27036124
DOI: 10.1042/BCJ20160254

実験手法

X-RAY DIFFRACTION (1.904 Å)