9GVQ

MUC5AC mucin amino acids 28 to 1483

9GVQ の概要

• エントリーDOI: 10.2210/pdb9gvq/pdb
• 関連するPDBエントリー: 9GVJ
• EMDBエントリー: 51639
• 分子名称: Mucin-5AC, CALCIUM ION, COPPER (II) ION (3 entities in total)
• 機能のキーワード: mucin, lung, filament, polymer, disulfide, protein fibril
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 629057.87

構造登録者

Haberman, M.,Kamyshinsky, R.,Fass, D. (登録日: 2024-09-25, 公開日: 2024-12-04, 最終更新日: 2025-03-19)

主引用文献

Haberman, M.,Kamyshinsky, R.,Reznik, N.,Yeshaya, N.,Khmelnitsky, L.,Plender, E.G.,Eichler, E.E.,Fass, D.
MUC5AC filaments illuminate the structural diversification of respiratory and intestinal mucins.
Proc.Natl.Acad.Sci.USA, 122:e2419717122-e2419717122, 2025

PubMed Abstract: Secreted mucins are multimegadalton glycoprotein polymers that share the function of protecting mucosal tissues but diversified for activities in different organs of the body. Structural studies of secreted mucins are complicated by the enormous sizes, flexibility, and complex supramolecular assembly modes of these glycoproteins. The two major respiratory mucins are MUC5AC and MUC5B. Here, we present structures of a large amino-terminal segment of MUC5AC in the form of helical filaments. These filaments differ from filamentous and tubular structures observed previously for the intestinal mucin MUC2 and the partial mucin homolog VWF. Nevertheless, the MUC5AC helical filaments support the proposed mechanism, based on MUC2 and VWF, for how noncovalent interactions between mucin monomers guide disulfide crosslinking to form polymers. The high-resolution MUC5AC structures show how local and limited changes in amino acid sequence can profoundly affect higher-order assembly while preserving the overall folds and polymerization activity of mucin glycoproteins. Differences in supramolecular assembly are likely to be functionally significant considering the divergence of mechanical properties and physiological requirements between respiratory and intestinal mucins. Determining the high-resolution structures of respiratory mucins provides a foundation for understanding the mechanisms by which they clean and protect the lungs. Moreover, the MUC5AC structure enables visualization of the sites of human amino acid sequence variation and disease-associated mutations.

PubMed: 40035770
DOI: 10.1073/pnas.2419717122

実験手法

ELECTRON MICROSCOPY (3.9 Å)