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TitleStructural characterization of atrial natriuretic peptide amyloid fibrils from patients with atrial fibrillation.
Journal, issue, pagesNat Commun, Vol. 16, Issue 1, Page 9556, Year 2025
Publish dateOct 29, 2025
AuthorsLuca Broggini / Marco Piccoli / Antonio Chaves-Sanjuan / Diane Marie Valérie Bonnet / Federica Cirillo / Cristina Visentin / Federica Sonzini / Paola Signorelli / Ivana Lavota / Melissa Milazzo / Simona Nonnis / Lorenzo Menicanti / Giuseppe Ciconte / Carlo Pappone / Luigi Anastasia / Stefano Ricagno /
PubMed AbstractIsolated 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). ...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.
External linksNat Commun / PubMed:41162370 / PubMed Central
MethodsEM (helical sym.)
Resolution2.96 - 3.3 Å
Structure data

53891

9rbd

EMDB-53891, PDB-9rbd:
Cryo-EM structure of ANP amyloids from left atrial appendage of atrial fibrillation patient - polymorph A
Method: EM (helical sym.) / Resolution: 2.96 Å

53910

9rbw

EMDB-53910, PDB-9rbw:
Cryo-EM structure of ANP amyloids from left atrial appendage of atrial fibrillation patient - polymorph B
Method: EM (helical sym.) / Resolution: 3.3 Å

Source
  • homo sapiens (human)
KeywordsPROTEIN FIBRIL / amyloid / cardiac amyloidosis / in vivo / aggregation

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