ATTRv-V30M amyloid fibrils from heart and nerves exhibit structural homogeneity.

ATTR V30M mutation cryo-EM helical reconstruction peripheral nerve fibrils systemic amyloidosis transthyretin amyloidosis

Journal

Structure (London, England : 1993)
ISSN: 1878-4186
Titre abrégé: Structure
Pays: United States
ID NLM: 101087697

Informations de publication

Date de publication:
09 Oct 2024
Historique:
received: 03 06 2024
revised: 07 08 2024
accepted: 23 09 2024
medline: 19 10 2024
pubmed: 19 10 2024
entrez: 18 10 2024
Statut: aheadofprint

Résumé

Amyloidogenic transthyretin (ATTR) amyloidosis is a systemic disease characterized by the deposition of amyloid fibrils made of transthyretin. Transthyretin is primarily produced in tetrameric form by the liver, but also by retinal epithelium and choroid plexus. The deposition of these fibrils in the myocardium and peripheral nerves causes cardiomyopathies and neuropathies, respectively. Using cryoelectron microscopy (cryo-EM), we investigated fibrils extracted from cardiac and nerve tissues of an ATTRv-V30M patient. We found consistent fibril structures from both tissues, similar to cardiac fibrils previously described, but different from vitreous humor fibrils of the same genotype. Our findings, along with previous ATTR fibrils structural studies, suggest a uniform fibrillar architecture across different tissues when transthyretin originates from the liver. This study advances our understanding of how deposition and production sites influence fibril structure in ATTRv-V30M amyloidosis.

Identifiants

DOI: 10.1016/j.str.2024.09.021 PMID: 39423808
pubmed: 39423808
pii: S0969-2126(24)00421-0
doi: 10.1016/j.str.2024.09.021
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2024 Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests L.S. consults for Intellia Therapeutics Inc. and Attralus Inc., and Advisory Board member for Alexion Pharmaceuticals.

Auteurs

Binh An Nguyen (BA)

Center for Alzheimer's and Neurodegenerative Diseases, University of Texas Southwestern Medical Center (UTSW), Dallas, TX 75390, USA; Department of Biophysics, University of Texas Southwestern Medical Center (UTSW), Dallas, TX 75390, USA; Peter O'Donnell Jr Brain Institute, University of Texas Southwestern Medical Center (UTSW), Dallas, TX 75390, USA.

Shumaila Afrin (S)

Center for Alzheimer's and Neurodegenerative Diseases, University of Texas Southwestern Medical Center (UTSW), Dallas, TX 75390, USA; Department of Biophysics, University of Texas Southwestern Medical Center (UTSW), Dallas, TX 75390, USA; Peter O'Donnell Jr Brain Institute, University of Texas Southwestern Medical Center (UTSW), Dallas, TX 75390, USA.

Anna Yakubovska (A)

Center for Alzheimer's and Neurodegenerative Diseases, University of Texas Southwestern Medical Center (UTSW), Dallas, TX 75390, USA; Department of Biophysics, University of Texas Southwestern Medical Center (UTSW), Dallas, TX 75390, USA; Peter O'Donnell Jr Brain Institute, University of Texas Southwestern Medical Center (UTSW), Dallas, TX 75390, USA.

Virender Singh (V)

Center for Alzheimer's and Neurodegenerative Diseases, University of Texas Southwestern Medical Center (UTSW), Dallas, TX 75390, USA; Department of Biophysics, University of Texas Southwestern Medical Center (UTSW), Dallas, TX 75390, USA; Peter O'Donnell Jr Brain Institute, University of Texas Southwestern Medical Center (UTSW), Dallas, TX 75390, USA.

Rose Pedretti (R)

Center for Alzheimer's and Neurodegenerative Diseases, University of Texas Southwestern Medical Center (UTSW), Dallas, TX 75390, USA; Department of Biophysics, University of Texas Southwestern Medical Center (UTSW), Dallas, TX 75390, USA; Peter O'Donnell Jr Brain Institute, University of Texas Southwestern Medical Center (UTSW), Dallas, TX 75390, USA.

Parker Bassett (P)

Center for Alzheimer's and Neurodegenerative Diseases, University of Texas Southwestern Medical Center (UTSW), Dallas, TX 75390, USA; Department of Biophysics, University of Texas Southwestern Medical Center (UTSW), Dallas, TX 75390, USA; Peter O'Donnell Jr Brain Institute, University of Texas Southwestern Medical Center (UTSW), Dallas, TX 75390, USA.

Maja Pekala (M)

Center for Alzheimer's and Neurodegenerative Diseases, University of Texas Southwestern Medical Center (UTSW), Dallas, TX 75390, USA; Department of Biophysics, University of Texas Southwestern Medical Center (UTSW), Dallas, TX 75390, USA; Peter O'Donnell Jr Brain Institute, University of Texas Southwestern Medical Center (UTSW), Dallas, TX 75390, USA.

Jaime Vaquer Alicea (JV)

Center for Alzheimer's and Neurodegenerative Diseases, University of Texas Southwestern Medical Center (UTSW), Dallas, TX 75390, USA; Peter O'Donnell Jr Brain Institute, University of Texas Southwestern Medical Center (UTSW), Dallas, TX 75390, USA.

Peter Kunach (P)

Center for Alzheimer's and Neurodegenerative Diseases, University of Texas Southwestern Medical Center (UTSW), Dallas, TX 75390, USA; Peter O'Donnell Jr Brain Institute, University of Texas Southwestern Medical Center (UTSW), Dallas, TX 75390, USA; Department of Neurology, McGill University, Montreal, Quebec H3A 2B4, Canada.

Lanie Wang (L)

Center for Alzheimer's and Neurodegenerative Diseases, University of Texas Southwestern Medical Center (UTSW), Dallas, TX 75390, USA; Department of Biophysics, University of Texas Southwestern Medical Center (UTSW), Dallas, TX 75390, USA; Peter O'Donnell Jr Brain Institute, University of Texas Southwestern Medical Center (UTSW), Dallas, TX 75390, USA.

Andrew Lemoff (A)

Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

Barbara Kluve-Beckerman (B)

Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA.

Lorena Saelices (L)

Center for Alzheimer's and Neurodegenerative Diseases, University of Texas Southwestern Medical Center (UTSW), Dallas, TX 75390, USA; Department of Biophysics, University of Texas Southwestern Medical Center (UTSW), Dallas, TX 75390, USA; Peter O'Donnell Jr Brain Institute, University of Texas Southwestern Medical Center (UTSW), Dallas, TX 75390, USA. Electronic address: lorena.saelicesgomez@utsouthwestern.edu.

Classifications MeSH