6TM6

MUC2 CysD1 domain

6TM6 の概要

• エントリーDOI: 10.2210/pdb6tm6/pdb
• 関連するPDBエントリー: 6TM2
• 分子名称: Mucin-2, CALCIUM ION (3 entities in total)
• 機能のキーワード: extracellular, polymer, cysd, mucin, calcium, disulfide, wxxw, structural protein
• 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: 10902.19

構造登録者

Khmelnitsky, L.,Fass, D. (登録日: 2019-12-03, 公開日: 2020-02-19, 最終更新日: 2024-11-13)

主引用文献

Javitt, G.,Khmelnitsky, L.,Albert, L.,Bigman, L.S.,Elad, N.,Morgenstern, D.,Ilani, T.,Levy, Y.,Diskin, R.,Fass, D.
Assembly Mechanism of Mucin and von Willebrand Factor Polymers.
Cell, 183:717-729.e16, 2020

PubMed Abstract: The respiratory and intestinal tracts are exposed to physical and biological hazards accompanying the intake of air and food. Likewise, the vasculature is threatened by inflammation and trauma. Mucin glycoproteins and the related von Willebrand factor guard the vulnerable cell layers in these diverse systems. Colon mucins additionally house and feed the gut microbiome. Here, we present an integrated structural analysis of the intestinal mucin MUC2. Our findings reveal the shared mechanism by which complex macromolecules responsible for blood clotting, mucociliary clearance, and the intestinal mucosal barrier form protective polymers and hydrogels. Specifically, cryo-electron microscopy and crystal structures show how disulfide-rich bridges and pH-tunable interfaces control successive assembly steps in the endoplasmic reticulum and Golgi apparatus. Remarkably, a densely O-glycosylated mucin domain performs an organizational role in MUC2. The mucin assembly mechanism and its adaptation for hemostasis provide the foundation for rational manipulation of barrier function and coagulation.

PubMed: 33031746
DOI: 10.1016/j.cell.2020.09.021

実験手法

X-RAY DIFFRACTION (1.63 Å)