9RBD

Cryo-EM structure of ANP amyloids from left atrial appendage of atrial fibrillation patient - polymorph A

9RBD の概要

• エントリーDOI: 10.2210/pdb9rbd/pdb
• EMDBエントリー: 53891
• 分子名称: Natriuretic peptides A (1 entity in total)
• 機能のキーワード: amyloid, cardiac amyloidosis, in vivo, aggregation, protein fibril
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 20
• 化学式量合計: 51457.64

構造登録者

Broggini, L.,Chaves-Sanjuan, A.,Ricagno, S. (登録日: 2025-05-22, 公開日: 2025-08-27, 最終更新日: 2025-11-12)

主引用文献

Broggini, L.,Piccoli, M.,Chaves-Sanjuan, A.,Bonnet, D.M.V.,Cirillo, F.,Visentin, C.,Sonzini, F.,Signorelli, P.,Lavota, I.,Milazzo, M.,Nonnis, S.,Menicanti, L.,Ciconte, G.,Pappone, C.,Anastasia, L.,Ricagno, S.
Structural characterization of atrial natriuretic peptide amyloid fibrils from patients with atrial fibrillation.
Nat Commun, 16:9556-9556, 2025

PubMed Abstract: Isolated atrial amyloidosis (IAA) is a localized cardiac disorder characterized by atrial natriuretic peptide (ANP) amyloids deposition in the atria, linked to aging and atrial fibrillation (AF). While monomeric ANP regulates blood pressure, its dimeric form is associated with cardiovascular conditions, including AF. The mechanistic link between ANP aggregation, IAA, and AF remains unclear. Here, we present the first high-resolution structural characterization of ANP fibrils extracted from AF patients, revealing two distinct fibril polymorphs. Both present covalent ANP dimers as building blocks but diverge in their structural architecture: one features antiparallel dimers stabilized by a single disulfide bond, while the other consists of parallel dimers bridged by two interchain disulfide bonds. These fibril morphologies were conserved across patients, suggesting a common aggregation mechanism in IAA. Overall, our findings ascribe to dimeric ANP a critical role in amyloid formation, offering promising directions for earlier detection and treatment of IAA.

PubMed: 41162370
DOI: 10.1038/s41467-025-64618-1

実験手法

ELECTRON MICROSCOPY (2.96 Å)