IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-44820-3.html
   My bibliography  Save this article

Structural polymorphism of amyloid fibrils in ATTR amyloidosis revealed by cryo-electron microscopy

Author

Listed:
  • Binh An Nguyen

    (Center for Alzheimer’s and Neurodegenerative Diseases, University of Texas Southwestern Medical Center (UTSW)
    University of Texas Southwestern Medical Center (UTSW)
    Peter O’Donnell Jr Brain Institute, University of Texas Southwestern Medical Center (UTSW))

  • Virender Singh

    (Center for Alzheimer’s and Neurodegenerative Diseases, University of Texas Southwestern Medical Center (UTSW)
    University of Texas Southwestern Medical Center (UTSW)
    Peter O’Donnell Jr Brain Institute, University of Texas Southwestern Medical Center (UTSW))

  • Shumaila Afrin

    (Center for Alzheimer’s and Neurodegenerative Diseases, University of Texas Southwestern Medical Center (UTSW)
    University of Texas Southwestern Medical Center (UTSW)
    Peter O’Donnell Jr Brain Institute, University of Texas Southwestern Medical Center (UTSW))

  • Anna Yakubovska

    (Center for Alzheimer’s and Neurodegenerative Diseases, University of Texas Southwestern Medical Center (UTSW)
    University of Texas Southwestern Medical Center (UTSW)
    Peter O’Donnell Jr Brain Institute, University of Texas Southwestern Medical Center (UTSW))

  • Lanie Wang

    (Center for Alzheimer’s and Neurodegenerative Diseases, University of Texas Southwestern Medical Center (UTSW)
    University of Texas Southwestern Medical Center (UTSW)
    Peter O’Donnell Jr Brain Institute, University of Texas Southwestern Medical Center (UTSW))

  • Yasmin Ahmed

    (Center for Alzheimer’s and Neurodegenerative Diseases, University of Texas Southwestern Medical Center (UTSW)
    University of Texas Southwestern Medical Center (UTSW)
    Peter O’Donnell Jr Brain Institute, University of Texas Southwestern Medical Center (UTSW))

  • Rose Pedretti

    (Center for Alzheimer’s and Neurodegenerative Diseases, University of Texas Southwestern Medical Center (UTSW)
    University of Texas Southwestern Medical Center (UTSW)
    Peter O’Donnell Jr Brain Institute, University of Texas Southwestern Medical Center (UTSW))

  • Maria del Carmen Fernandez-Ramirez

    (Center for Alzheimer’s and Neurodegenerative Diseases, University of Texas Southwestern Medical Center (UTSW)
    University of Texas Southwestern Medical Center (UTSW)
    Peter O’Donnell Jr Brain Institute, University of Texas Southwestern Medical Center (UTSW))

  • Preeti Singh

    (Center for Alzheimer’s and Neurodegenerative Diseases, University of Texas Southwestern Medical Center (UTSW)
    University of Texas Southwestern Medical Center (UTSW)
    Peter O’Donnell Jr Brain Institute, University of Texas Southwestern Medical Center (UTSW))

  • Maja Pękała

    (Center for Alzheimer’s and Neurodegenerative Diseases, University of Texas Southwestern Medical Center (UTSW)
    University of Texas Southwestern Medical Center (UTSW)
    Peter O’Donnell Jr Brain Institute, University of Texas Southwestern Medical Center (UTSW))

  • Luis O. Cabrera Hernandez

    (Center for Alzheimer’s and Neurodegenerative Diseases, University of Texas Southwestern Medical Center (UTSW)
    University of Texas Southwestern Medical Center (UTSW)
    Peter O’Donnell Jr Brain Institute, University of Texas Southwestern Medical Center (UTSW))

  • Siddharth Kumar

    (Center for Alzheimer’s and Neurodegenerative Diseases, University of Texas Southwestern Medical Center (UTSW)
    University of Texas Southwestern Medical Center (UTSW)
    Peter O’Donnell Jr Brain Institute, University of Texas Southwestern Medical Center (UTSW))

  • Andrew Lemoff

    (University of Texas Southwestern Medical Center)

  • Roman Gonzalez-Prieto

    (Andalusian Center for Molecular Biology and regenerative Medicine (CABIMER), Universidad de Sevilla-CSIC-Universidad-Pablo de Olavide, Departmento de Biología Celular, Facultad de Biología, Universidad de Sevilla)

  • Michael R. Sawaya

    (University of California, Los Angeles, Howard Hughes Medical Institute)

  • David S. Eisenberg

    (University of California, Los Angeles, Howard Hughes Medical Institute)

  • Merrill Douglas Benson

    (Indiana University School of Medicine)

  • Lorena Saelices

    (Center for Alzheimer’s and Neurodegenerative Diseases, University of Texas Southwestern Medical Center (UTSW)
    University of Texas Southwestern Medical Center (UTSW)
    Peter O’Donnell Jr Brain Institute, University of Texas Southwestern Medical Center (UTSW))

Abstract

ATTR amyloidosis is caused by the deposition of transthyretin in the form of amyloid fibrils in virtually every organ of the body, including the heart. This systemic deposition leads to a phenotypic variability that has not been molecularly explained yet. In brain amyloid conditions, previous studies suggest an association between clinical phenotype and the molecular structures of their amyloid fibrils. Here we investigate whether there is such an association in ATTRv amyloidosis patients carrying the mutation I84S. Using cryo-electron microscopy, we determined the structures of cardiac fibrils extracted from three ATTR amyloidosis patients carrying the ATTRv-I84S mutation, associated with a consistent clinical phenotype. We found that in each ATTRv-I84S patient, the cardiac fibrils exhibited different local conformations, and these variations can co-exist within the same fibril. Our finding suggests that one amyloid disease may associate with multiple fibril structures in systemic amyloidoses, calling for further studies.

Suggested Citation

  • Binh An Nguyen & Virender Singh & Shumaila Afrin & Anna Yakubovska & Lanie Wang & Yasmin Ahmed & Rose Pedretti & Maria del Carmen Fernandez-Ramirez & Preeti Singh & Maja Pękała & Luis O. Cabrera Herna, 2024. "Structural polymorphism of amyloid fibrils in ATTR amyloidosis revealed by cryo-electron microscopy," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-44820-3
    DOI: 10.1038/s41467-024-44820-3
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-44820-3
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-024-44820-3?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Irina Iakovleva & Michael Hall & Melanie Oelker & Linda Sandblad & Intissar Anan & A. Elisabeth Sauer-Eriksson, 2021. "Structural basis for transthyretin amyloid formation in vitreous body of the eye," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    2. Matthias Schmidt & Sebastian Wiese & Volkan Adak & Jonas Engler & Shubhangi Agarwal & Günter Fritz & Per Westermark & Martin Zacharias & Marcus Fändrich, 2019. "Cryo-EM structure of a transthyretin-derived amyloid fibril from a patient with hereditary ATTR amyloidosis," Nature Communications, Nature, vol. 10(1), pages 1-9, December.
    3. Benjamin Falcon & Wenjuan Zhang & Alexey G. Murzin & Garib Murshudov & Holly J. Garringer & Ruben Vidal & R. Anthony Crowther & Bernardino Ghetti & Sjors H. W. Scheres & Michel Goedert, 2018. "Structures of filaments from Pick’s disease reveal a novel tau protein fold," Nature, Nature, vol. 561(7721), pages 137-140, September.
    4. Sjors H. W. Scheres & Benjamin Ryskeldi-Falcon & Michel Goedert, 2023. "Molecular pathology of neurodegenerative diseases by cryo-EM of amyloids," Nature, Nature, vol. 621(7980), pages 701-710, September.
    5. Lynn Radamaker & Julian Baur & Stefanie Huhn & Christian Haupt & Ute Hegenbart & Stefan Schönland & Akanksha Bansal & Matthias Schmidt & Marcus Fändrich, 2021. "Cryo-EM reveals structural breaks in a patient-derived amyloid fibril from systemic AL amyloidosis," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    6. Maximilian Steinebrei & Juliane Gottwald & Julian Baur & Christoph Röcken & Ute Hegenbart & Stefan Schönland & Matthias Schmidt, 2022. "Cryo-EM structure of an ATTRwt amyloid fibril from systemic non-hereditary transthyretin amyloidosis," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
    7. Falk Liberta & Sarah Loerch & Matthies Rennegarbe & Angelika Schierhorn & Per Westermark & Gunilla T. Westermark & Bouke P. C. Hazenberg & Nikolaus Grigorieff & Marcus Fändrich & Matthias Schmidt, 2019. "Cryo-EM fibril structures from systemic AA amyloidosis reveal the species complementarity of pathological amyloids," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
    8. Sambhasan Banerjee & Julian Baur & Christoph Daniel & Peter Benedikt Pfeiffer & Manuel Hitzenberger & Lukas Kuhn & Sebastian Wiese & Johan Bijzet & Christian Haupt & Kerstin U. Amann & Martin Zacharia, 2022. "Amyloid fibril structure from the vascular variant of systemic AA amyloidosis," Nature Communications, Nature, vol. 13(1), pages 1-8, December.
    9. Yang Shi & Wenjuan Zhang & Yang Yang & Alexey G. Murzin & Benjamin Falcon & Abhay Kotecha & Mike Beers & Airi Tarutani & Fuyuki Kametani & Holly J. Garringer & Ruben Vidal & Grace I. Hallinan & Tammar, 2021. "Structure-based classification of tauopathies," Nature, Nature, vol. 598(7880), pages 359-363, October.
    10. Diana Arseni & Masato Hasegawa & Alexey G. Murzin & Fuyuki Kametani & Makoto Arai & Mari Yoshida & Benjamin Ryskeldi-Falcon, 2022. "Structure of pathological TDP-43 filaments from ALS with FTLD," Nature, Nature, vol. 601(7891), pages 139-143, January.
    11. Yi Xiao Jiang & Qin Cao & Michael R. Sawaya & Romany Abskharon & Peng Ge & Michael DeTure & Dennis W. Dickson & Janine Y. Fu & Rachel R. Ogorzalek Loo & Joseph A. Loo & David S. Eisenberg, 2022. "Amyloid fibrils in FTLD-TDP are composed of TMEM106B and not TDP-43," Nature, Nature, vol. 605(7909), pages 304-309, May.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Maximilian Steinebrei & Julian Baur & Anaviggha Pradhan & Niklas Kupfer & Sebastian Wiese & Ute Hegenbart & Stefan O. Schönland & Matthias Schmidt & Marcus Fändrich, 2023. "Common transthyretin-derived amyloid fibril structures in patients with hereditary ATTR amyloidosis," Nature Communications, Nature, vol. 14(1), pages 1-8, December.
    2. Sara Karimi-Farsijani & Kartikay Sharma & Marijana Ugrina & Lukas Kuhn & Peter Benedikt Pfeiffer & Christian Haupt & Sebastian Wiese & Ute Hegenbart & Stefan O. Schönland & Nadine Schwierz & Matthias , 2024. "Cryo-EM structure of a lysozyme-derived amyloid fibril from hereditary amyloidosis," Nature Communications, Nature, vol. 15(1), pages 1-9, December.
    3. Kartikay Sharma & Fabian Stockert & Jayakrishna Shenoy & Mélanie Berbon & Muhammed Bilal Abdul-Shukkoor & Birgit Habenstein & Antoine Loquet & Matthias Schmidt & Marcus Fändrich, 2024. "Cryo-EM observation of the amyloid key structure of polymorphic TDP-43 amyloid fibrils," Nature Communications, Nature, vol. 15(1), pages 1-8, December.
    4. Sara Karimi-Farsijani & Peter Benedikt Pfeiffer & Sambhasan Banerjee & Julian Baur & Lukas Kuhn & Niklas Kupfer & Ute Hegenbart & Stefan O. Schönland & Sebastian Wiese & Christian Haupt & Matthias Sch, 2024. "Light chain mutations contribute to defining the fibril morphology in systemic AL amyloidosis," Nature Communications, Nature, vol. 15(1), pages 1-8, December.
    5. Maximilian Steinebrei & Juliane Gottwald & Julian Baur & Christoph Röcken & Ute Hegenbart & Stefan Schönland & Matthias Schmidt, 2022. "Cryo-EM structure of an ATTRwt amyloid fibril from systemic non-hereditary transthyretin amyloidosis," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
    6. Martin Wilkinson & Rodrigo U. Gallardo & Roberto Maya Martinez & Nicolas Guthertz & Masatomo So & Liam D. Aubrey & Sheena E. Radford & Neil A. Ranson, 2023. "Disease-relevant β2-microglobulin variants share a common amyloid fold," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    7. Tim Schulte & Antonio Chaves-Sanjuan & Valentina Speranzini & Kevin Sicking & Melissa Milazzo & Giulia Mazzini & Paola Rognoni & Serena Caminito & Paolo Milani & Chiara Marabelli & Alessandro Corbelli, 2024. "Helical superstructures between amyloid and collagen in cardiac fibrils from a patient with AL amyloidosis," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    8. Sambhasan Banerjee & Julian Baur & Christoph Daniel & Peter Benedikt Pfeiffer & Manuel Hitzenberger & Lukas Kuhn & Sebastian Wiese & Johan Bijzet & Christian Haupt & Kerstin U. Amann & Martin Zacharia, 2022. "Amyloid fibril structure from the vascular variant of systemic AA amyloidosis," Nature Communications, Nature, vol. 13(1), pages 1-8, December.
    9. Irina Iakovleva & Michael Hall & Melanie Oelker & Linda Sandblad & Intissar Anan & A. Elisabeth Sauer-Eriksson, 2021. "Structural basis for transthyretin amyloid formation in vitreous body of the eye," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    10. Szymon W. Manka & Wenjuan Zhang & Adam Wenborn & Jemma Betts & Susan Joiner & Helen R. Saibil & John Collinge & Jonathan D. F. Wadsworth, 2022. "2.7 Å cryo-EM structure of ex vivo RML prion fibrils," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    11. Pijush Chakraborty & Gwladys Rivière & Alina Hebestreit & Alain Ibáñez Opakua & Ina M. Vorberg & Loren B. Andreas & Markus Zweckstetter, 2023. "Acetylation discriminates disease-specific tau deposition," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    12. Gregory E. Merz & Matthew J. Chalkley & Sophia K. Tan & Eric Tse & Joanne Lee & Stanley B. Prusiner & Nick A. Paras & William F. DeGrado & Daniel R. Southworth, 2023. "Stacked binding of a PET ligand to Alzheimer’s tau paired helical filaments," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    13. Nikolaos Louros & Meine Ramakers & Emiel Michiels & Katerina Konstantoulea & Chiara Morelli & Teresa Garcia & Nele Moonen & Sam D’Haeyer & Vera Goossens & Dietmar Rudolf Thal & Dominique Audenaert & F, 2022. "Mapping the sequence specificity of heterotypic amyloid interactions enables the identification of aggregation modifiers," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    14. Itika Saha & Patricia Yuste-Checa & Miguel Silva Padilha & Qiang Guo & Roman Körner & Hauke Holthusen & Victoria A. Trinkaus & Irina Dudanova & Rubén Fernández-Busnadiego & Wolfgang Baumeister & David, 2023. "The AAA+ chaperone VCP disaggregates Tau fibrils and generates aggregate seeds in a cellular system," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    15. Nicolai Franzmeier & Matthias Brendel & Leonie Beyer & Luna Slemann & Gabor G. Kovacs & Thomas Arzberger & Carolin Kurz & Gesine Respondek & Milica J. Lukic & Davina Biel & Anna Rubinski & Lukas Front, 2022. "Tau deposition patterns are associated with functional connectivity in primary tauopathies," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    16. Luca Pinzi & Christian Conze & Nicolo Bisi & Gabriele Dalla Torre & Ahmed Soliman & Nanci Monteiro-Abreu & Nataliya I. Trushina & Andrea Krusenbaum & Maryam Khodaei Dolouei & Andrea Hellwig & Michael , 2024. "Quantitative live cell imaging of a tauopathy model enables the identification of a polypharmacological drug candidate that restores physiological microtubule interaction," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    17. Galina Limorenko & Meltem Tatli & Rajasekhar Kolla & Sergey Nazarov & Marie-Theres Weil & David C. Schöndorf & Daniela Geist & Peter Reinhardt & Dagmar E. Ehrnhoefer & Henning Stahlberg & Laura Gaspar, 2023. "Fully co-factor-free ClearTau platform produces seeding-competent Tau fibrils for reconstructing pathological Tau aggregates," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    18. Li-Qiang Wang & Yeyang Ma & Han-Ye Yuan & Kun Zhao & Mu-Ya Zhang & Qiang Wang & Xi Huang & Wen-Chang Xu & Bin Dai & Jie Chen & Dan Li & Delin Zhang & Zhengzhi Wang & Liangyu Zou & Ping Yin & Cong Liu , 2022. "Cryo-EM structure of an amyloid fibril formed by full-length human SOD1 reveals its conformational conversion," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    19. Vishruth Mullapudi & Jaime Vaquer-Alicea & Vaibhav Bommareddy & Anthony R. Vega & Bryan D. Ryder & Charles L. White & Marc. I. Diamond & Lukasz A. Joachimiak, 2023. "Network of hotspot interactions cluster tau amyloid folds," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    20. Nikolaos Louros & Martin Wilkinson & Grigoria Tsaka & Meine Ramakers & Chiara Morelli & Teresa Garcia & Rodrigo Gallardo & Sam D’Haeyer & Vera Goossens & Dominique Audenaert & Dietmar Rudolf Thal & Ia, 2024. "Local structural preferences in shaping tau amyloid polymorphism," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-44820-3. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.