Browsing by Author "Kunach, Peter"

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    ATTRv-V30M Type A amyloid fibrils from heart and nerves exhibit structural homogeneity
    (bioRxiv, 2024-05-14) Nguyen, Binh An; Afrin, Shumaila; Yakubovska, Anna; Singh, Virender; Alicea, Jaime Vaquer; Kunach, Peter; Singh, Preeti; Pekala, Maja; Ahmed, Yasmin; Fernandez-Ramirez, Maria del Carmen; Cabrera Hernandez, Luis O.; Pedretti, Rose; Bassett, Parker; Wang, Lanie; Lemoff, Andrew; Villalon, Layla; Kluve-Beckerman, Barbara; Saelices, Lorena; Pathology and Laboratory Medicine, School of Medicine
    ATTR amyloidosis is a systemic disease characterized by the deposition of amyloid fibrils made of transthyretin, a protein integral to transporting retinol and thyroid hormones. Transthyretin is primarily produced by the liver and circulates in blood as a tetramer. The retinal epithelium also secretes transthyretin, which is secreted to the vitreous humor of the eye. Because of mutations or aging, transthyretin can dissociate into amyloidogenic monomers triggering amyloid fibril formation. The deposition of transthyretin amyloid fibrils in the myocardium and peripheral nerves causes cardiomyopathies and neuropathies, respectively. Using cryo-electron microscopy, here we determined the structures of amyloid fibrils extracted from cardiac and nerve tissues of an ATTRv-V30M patient. We found that fibrils from both tissues share a consistent structural conformation, similar to the previously described structure of cardiac fibrils from an individual with the same genotype, but different from the fibril structure obtained from the vitreous humor. Our study hints to a uniform fibrillar architecture across different tissues within the same individual, only when the source of transthyretin is the liver. Moreover, this study provides the first description of ATTR fibrils from the nerves of a patient and enhances our understanding of the role of deposition site and protein production site in shaping the fibril structure in ATTRv-V30M amyloidosis.