7AUW

Inhibitory complex of human meprin beta with mouse fetuin-B.

7AUW の概要

• エントリーDOI: 10.2210/pdb7auw/pdb
• 分子名称: Meprin A subunit beta, alpha-L-fucopyranose-(1-3)-[2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)]2-acetamido-2-deoxy-beta-D-glucopyranose, SODIUM ION, ... (15 entities in total)
• 機能のキーワード: protease inhibitor complex, zinc metallopeptidase, cystatin-type modules, hydrolase, hydrolase inhibitor
• 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: 228924.81

構造登録者

Eckhard, U.,Gomis-Ruth, F.X. (登録日: 2020-11-03, 公開日: 2021-04-14, 最終更新日: 2024-10-16)

主引用文献

Eckhard, U.,Korschgen, H.,von Wiegen, N.,Stocker, W.,Gomis-Ruth, F.X.
The crystal structure of a 250-kDa heterotetrameric particle explains inhibition of sheddase meprin beta by endogenous fetuin-B.
Proc.Natl.Acad.Sci.USA, 118:-, 2021

PubMed Abstract: Meprin β (Mβ) is a multidomain type-I membrane metallopeptidase that sheds membrane-anchored substrates, releasing their soluble forms. Fetuin-B (FB) is its only known endogenous protein inhibitor. Herein, we analyzed the interaction between the ectodomain of Mβ (MβΔC) and FB, which stabilizes the enzyme and inhibits it with subnanomolar affinity. The MβΔC:FB crystal structure reveals a ∼250-kDa, ∼160-Å polyglycosylated heterotetrameric particle with a remarkable glycan structure. Two FB moieties insert like wedges through a "CPDCP trunk" and two hairpins into the respective peptidase catalytic domains, blocking the catalytic zinc ions through an "aspartate switch" mechanism. Uniquely, the active site clefts are obstructed from subsites S to S', but S and S' are spared, which prevents cleavage. Modeling of full-length Mβ reveals an EGF-like domain between MβΔC and the transmembrane segment that likely serves as a hinge to transit between membrane-distal and membrane-proximal conformations for inhibition and catalysis, respectively.

PubMed: 33782129
DOI: 10.1073/pnas.2023839118

実験手法

X-RAY DIFFRACTION (2.8 Å)