IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v12y2021i1d10.1038_s41467-021-27481-4.html
   My bibliography  Save this article

Structural basis for transthyretin amyloid formation in vitreous body of the eye

Author

Listed:
  • Irina Iakovleva

    (Umeå University)

  • Michael Hall

    (Umeå University)

  • Melanie Oelker

    (Umeå University)

  • Linda Sandblad

    (Umeå University)

  • Intissar Anan

    (Umeå University
    Wallenberg Centre for Molecular Medicine, Umeå University)

  • A. Elisabeth Sauer-Eriksson

    (Umeå University)

Abstract

Amyloid transthyretin (ATTR) amyloidosis is characterized by the abnormal accumulation of ATTR fibrils in multiple organs. However, the structure of ATTR fibrils from the eye is poorly understood. Here, we used cryo-EM to structurally characterize vitreous body ATTR fibrils. These structures were distinct from previously characterized heart fibrils, even though both have the same mutation and type A pathology. Differences were observed at several structural levels: in both the number and arrangement of protofilaments, and the conformation of the protein fibril in each layer of protofilaments. Thus, our results show that ATTR protein structure and its assembly into protofilaments in the type A fibrils can vary between patients carrying the same mutation. By analyzing and matching the interfaces between the amino acids in the ATTR fibril with those in the natively folded TTR, we are able to propose a mechanism for the structural conversion of TTR into a fibrillar form.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27481-4
    DOI: 10.1038/s41467-021-27481-4
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-021-27481-4
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-021-27481-4?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. Lynn Radamaker & Yin-Hsi Lin & Karthikeyan Annamalai & Stefanie Huhn & Ute Hegenbart & Stefan O. Schönland & Günter Fritz & Matthias Schmidt & Marcus Fändrich, 2019. "Cryo-EM structure of a light chain-derived amyloid fibril from a patient with systemic AL amyloidosis," Nature Communications, Nature, vol. 10(1), pages 1-8, 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. 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.
    4. Ai Woon Yee & Matteo Aldeghi & Matthew P. Blakeley & Andreas Ostermann & Philippe J. Mas & Martine Moulin & Daniele de Sanctis & Matthew W. Bowler & Christoph Mueller-Dieckmann & Edward P. Mitchell & , 2019. "A molecular mechanism for transthyretin amyloidogenesis," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
    5. Benjamin Falcon & Jasenko Zivanov & Wenjuan Zhang & Alexey G. Murzin & Holly J. Garringer & Ruben Vidal & R. Anthony Crowther & Kathy L. Newell & Bernardino Ghetti & Michel Goedert & Sjors H. W. Scher, 2019. "Novel tau filament fold in chronic traumatic encephalopathy encloses hydrophobic molecules," Nature, Nature, vol. 568(7752), pages 420-423, April.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    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. 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.
    3. Robert Bücker & Carolin Seuring & Cornelia Cazey & Katharina Veith & Maria García-Alai & Kay Grünewald & Meytal Landau, 2022. "The Cryo-EM structures of two amphibian antimicrobial cross-β amyloid fibrils," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    4. 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.

    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. 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.
    2. Emily G. Saccuzzo & Mubark D. Mebrat & Hailee F. Scelsi & Minjoo Kim & Minh Thu Ma & Xinya Su & Shannon E. Hill & Elisa Rheaume & Renhao Li & Matthew P. Torres & James C. Gumbart & Wade D. Van Horn & , 2024. "Competition between inside-out unfolding and pathogenic aggregation in an amyloid-forming β-propeller," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    3. 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.
    4. 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.
    5. 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.
    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. 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.
    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. Stephen J. Klawa & Michelle Lee & Kyle D. Riker & Tengyue Jian & Qunzhao Wang & Yuan Gao & Margaret L. Daly & Shreeya Bhonge & W. Seth Childers & Tolulope O. Omosun & Anil K. Mehta & David G. Lynn & R, 2024. "Uncovering supramolecular chirality codes for the design of tunable biomaterials," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    10. 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.
    11. Bote Qi & Shuting Jin & Hongsheng Qian & Yu Zou, 2020. "Bibliometric Analysis of Chronic Traumatic Encephalopathy Research from 1999 to 2019," IJERPH, MDPI, vol. 17(15), pages 1-15, July.
    12. Pamina Kazman & Ramona M. Absmeier & Harald Engelhardt & Johannes Buchner, 2021. "Dissection of the amyloid formation pathway in AL amyloidosis," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    13. Tim Schulte & Antonio Chaves-Sanjuan & Giulia Mazzini & Valentina Speranzini & Francesca Lavatelli & Filippo Ferri & Carlo Palizzotto & Maria Mazza & Paolo Milani & Mario Nuvolone & Anne-Cathrine Vogt, 2022. "Cryo-EM structure of ex vivo fibrils associated with extreme AA amyloidosis prevalence in a cat shelter," Nature Communications, Nature, vol. 13(1), pages 1-9, 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:12:y:2021:i:1:d:10.1038_s41467-021-27481-4. 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.