4GWM

Crystal structure of human promeprin beta

4GWM の概要

• エントリーDOI: 10.2210/pdb4gwm/pdb
• 関連するPDBエントリー: 4GWN
• 分子名称: Meprin A subunit beta, SODIUM ION, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (14 entities in total)
• 機能のキーワード: mulidomain structure, hydrolase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cell membrane ; Single-pass type I membrane protein: Q16820
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 143873.59

構造登録者

Arolas, J.L.,Broder, C.,Jefferson, T.,Guevara, T.,Sterchi, E.E.,Bode, W.,Stocker, W.,Becker-Pauly, C.,Gomis-Ruth, F.X. (登録日: 2012-09-03, 公開日: 2012-09-19, 最終更新日: 2024-10-30)

主引用文献

Arolas, J.L.,Broder, C.,Jefferson, T.,Guevara, T.,Sterchi, E.E.,Bode, W.,Stocker, W.,Becker-Pauly, C.,Gomis-Ruth, F.X.
Structural basis for the sheddase function of human meprin beta metalloproteinase at the plasma membrane
Proc.Natl.Acad.Sci.USA, 109:16131-16136, 2012

PubMed Abstract: Ectodomain shedding at the cell surface is a major mechanism to regulate the extracellular and circulatory concentration or the activities of signaling proteins at the plasma membrane. Human meprin β is a 145-kDa disulfide-linked homodimeric multidomain type-I membrane metallopeptidase that sheds membrane-bound cytokines and growth factors, thereby contributing to inflammatory diseases, angiogenesis, and tumor progression. In addition, it cleaves amyloid precursor protein (APP) at the β-secretase site, giving rise to amyloidogenic peptides. We have solved the X-ray crystal structure of a major fragment of the meprin β ectoprotein, the first of a multidomain oligomeric transmembrane sheddase, and of its zymogen. The meprin β dimer displays a compact shape, whose catalytic domain undergoes major rearrangement upon activation, and reveals an exosite and a sugar-rich channel, both of which possibly engage in substrate binding. A plausible structure-derived working mechanism suggests that substrates such as APP are shed close to the plasma membrane surface following an "N-like" chain trace.

PubMed: 22988105
DOI: 10.1073/pnas.1211076109

実験手法

X-RAY DIFFRACTION (1.85 Å)