2M2F

The membran-proximal domain of ADAM17

2M2F の概要

• エントリーDOI: 10.2210/pdb2m2f/pdb
• NMR情報: BMRB: 18912
• 分子名称: Disintegrin and metalloproteinase domain-containing protein 17 (1 entity in total)
• 機能のキーワード: adam17, membrane-proximal domain, hydrolase regulator, closed conformer
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Membrane; Single-pass type I membrane protein: P78536
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 9905.12

構造登録者

Duesterhoeft, S.,Jung, S.,Hung, C.,Tholey, A.,Soennichsen, F.D.,Groetzinger, J.,Lorenzen, I. (登録日: 2012-12-20, 公開日: 2013-04-10, 最終更新日: 2024-11-06)

主引用文献

Dusterhoft, S.,Jung, S.,Hung, C.W.,Tholey, A.,Sonnichsen, F.D.,Grotzinger, J.,Lorenzen, I.
Membrane-proximal domain of a disintegrin and metalloprotease-17 represents the putative molecular switch of its shedding activity operated by protein-disulfide isomerase.
J.Am.Chem.Soc., 135:5776-5781, 2013

PubMed Abstract: A disintegrin and metalloprotease-17 (ADAM17) is a major sheddase responsible for the regulation of a wide range of biological processes, like cellular differentiation, regeneration, or cancer progression. Hitherto, the mechanism regulating the enzymatic activity of ADAM17 is poorly understood. Recently, protein-disulfide isomerase (PDI) was shown to interact with ADAM17 and to down-regulate its enzymatic activity. Here we demonstrate by NMR spectroscopy and tandem-mass spectrometry that PDI directly interacts with the membrane-proximal domain (MPD), a domain of ADAM17 involved in its dimerization and substrate recognition. PDI catalyzes an isomerization of disulfide bridges within the thioredoxin motif C600XXC603 of the MPD and results in a drastic structural change between an active open state and an inactive closed conformation. This conformational change of the MPD putatively acts as a molecular switch, facilitating a global reorientation of the extracellular domains in ADAM17 and regulating its shedding activity.

PubMed: 23521534
DOI: 10.1021/ja400340u

実験手法

SOLUTION NMR