8S3O

Structure of native human CD109

8S3O の概要

• エントリーDOI: 10.2210/pdb8s3o/pdb
• EMDBエントリー: 19699
• 分子名称: CD109 antigen, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• 機能のキーワード: protease inhibitor, native conformation, alfa-macroglobulin, immune system
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 163584.76

構造登録者

Almeida, V.A.,Andersen, G.R. (登録日: 2024-02-20, 公開日: 2025-03-05, 最終更新日: 2025-09-17)

主引用文献

Almeida, A.V.,Jensen, K.T.,Harwood, S.L.,Jorgensen, M.H.,Nielsen, N.S.,Thogersen, I.B.,Enghild, J.J.,Andersen, G.R.
Three cryo-EM structures of CD109 reveal its mechanism of protease inhibition.
Cell Rep, 44:115787-115787, 2025

PubMed Abstract: CD109 is a glycosylphosphatidylinositol-anchored protein. In addition to regulating transforming growth factor β (TGF-β) network signaling, CD109 is also a protease inhibitor. Protease cleavage of its bait region triggers a conformational change releasing the major fragment from the cell surface, exposing a reactive thioester that can conjugate proteases. To understand this protease inhibition mechanism, we determined cryoelectron microscopy structures of CD109 in native, protease-activated, and methylamine-activated conformations. Despite CD109's low sequence similarity with the protease inhibitor A2ML1, CD109 adopts a similar protease-activated conformation, suggesting a shared mechanism of protease inhibition. Deglycosylation of CD109 does not affect chymotrypsin conjugation but enhances substrate access, suggesting that CD109 glycans contribute to protease inhibition. Our data provide a structural basis for understanding CD109's protease-triggered membrane release, its protease inhibitory mechanism, and additional biological functions.

PubMed: 40482031
DOI: 10.1016/j.celrep.2025.115787

実験手法

ELECTRON MICROSCOPY (2.99 Å)