IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-50686-2.html
   My bibliography  Save this article

Helical superstructures between amyloid and collagen in cardiac fibrils from a patient with AL amyloidosis

Author

Listed:
  • Tim Schulte

    (IRCCS Policlinico San Donato
    Stockholm University)

  • Antonio Chaves-Sanjuan

    (Università degli Studi di Milano)

  • Valentina Speranzini

    (Università degli Studi di Milano)

  • Kevin Sicking

    (Institute for Neuropathology
    Aligning Science Across Parkinson’s (ASAP) Collaborative Research Network)

  • Melissa Milazzo

    (Università degli Studi di Milano)

  • Giulia Mazzini

    (Università Degli Studi di Pavia)

  • Paola Rognoni

    (Università Degli Studi di Pavia)

  • Serena Caminito

    (Università Degli Studi di Pavia)

  • Paolo Milani

    (Università Degli Studi di Pavia)

  • Chiara Marabelli

    (Università degli Studi di Milano)

  • Alessandro Corbelli

    (Istituto di Ricerche Farmacologiche Mario Negri IRCCS)

  • Luisa Diomede

    (Istituto di Ricerche Farmacologiche Mario Negri IRCCS)

  • Fabio Fiordaliso

    (Istituto di Ricerche Farmacologiche Mario Negri IRCCS)

  • Luigi Anastasia

    (IRCCS Policlinico San Donato
    Vita-Salute San Raffaele University)

  • Carlo Pappone

    (IRCCS Policlinico San Donato
    Vita-Salute San Raffaele University
    San Donato)

  • Giampaolo Merlini

    (Università Degli Studi di Pavia)

  • Martino Bolognesi

    (Università degli Studi di Milano)

  • Mario Nuvolone

    (Università Degli Studi di Pavia)

  • Rubén Fernández-Busnadiego

    (Institute for Neuropathology
    Aligning Science Across Parkinson’s (ASAP) Collaborative Research Network
    University of Göttingen
    University of Göttingen)

  • Giovanni Palladini

    (Università Degli Studi di Pavia)

  • Stefano Ricagno

    (IRCCS Policlinico San Donato
    Università degli Studi di Milano)

Abstract

Systemic light chain (LC) amyloidosis (AL) is a disease where organs are damaged by an overload of a misfolded patient-specific antibody-derived LC, secreted by an abnormal B cell clone. The high LC concentration in the blood leads to amyloid deposition at organ sites. Indeed, cryogenic electron microscopy (cryo-EM) has revealed unique amyloid folds for heart-derived fibrils taken from different patients. Here, we present the cryo-EM structure of heart-derived AL amyloid (AL59) from another patient with severe cardiac involvement. The double-layered structure displays a u-shaped core that is closed by a β-arc lid and extended by a straight tail. Noteworthy, the fibril harbours an extended constant domain fragment, thus ruling out the variable domain as sole amyloid building block. Surprisingly, the fibrils were abundantly concatenated with a proteinaceous polymer, here identified as collagen VI (COLVI) by immuno-electron microscopy (IEM) and mass-spectrometry. Cryogenic electron tomography (cryo-ET) showed how COLVI wraps around the amyloid forming a helical superstructure, likely stabilizing and protecting the fibrils from clearance. Thus, here we report structural evidence of interactions between amyloid and collagen, potentially signifying a distinct pathophysiological mechanism of amyloid deposits.

Suggested Citation

  • 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.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50686-2
    DOI: 10.1038/s41467-024-50686-2
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-50686-2
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-024-50686-2?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. Yun-Tao Liu & Heng Zhang & Hui Wang & Chang-Lu Tao & Guo-Qiang Bi & Z. Hong Zhou, 2022. "Isotropic reconstruction for electron tomography with deep learning," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    2. Paolo Swuec & Francesca Lavatelli & Masayoshi Tasaki & Cristina Paissoni & Paola Rognoni & Martina Maritan & Francesca Brambilla & Paolo Milani & Pierluigi Mauri & Carlo Camilloni & Giovanni Palladini, 2019. "Cryo-EM structure of cardiac amyloid fibrils from an immunoglobulin light chain AL amyloidosis patient," Nature Communications, Nature, vol. 10(1), pages 1-9, December.
    3. 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.
    4. 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.
    5. 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.
    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. 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.
    2. 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.
    3. 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.
    4. 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.
    5. 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.
    6. 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.
    7. Lynn Radamaker & Sara Karimi-Farsijani & Giada Andreotti & Julian Baur & Matthias Neumann & Sarah Schreiner & Natalie Berghaus & Raoul Motika & Christian Haupt & Paul Walther & Volker Schmidt & Stefan, 2021. "Role of mutations and post-translational modifications in systemic AL amyloidosis studied by cryo-EM," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    8. Simon Wiedemann & Reinhard Heckel, 2024. "A deep learning method for simultaneous denoising and missing wedge reconstruction in cryogenic electron tomography," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    9. 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.
    10. Bryan S. Sibert & Joseph Y. Kim & Jie E. Yang & Zunlong Ke & Christopher C. Stobart & Martin L. Moore & Elizabeth R. Wright, 2024. "Assembly of respiratory syncytial virus matrix protein lattice and its coordination with fusion glycoprotein trimers," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    11. 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.
    12. Zhen Hou & Frank Nightingale & Yanan Zhu & Craig MacGregor-Chatwin & Peijun Zhang, 2023. "Structure of native chromatin fibres revealed by Cryo-ET in situ," Nature Communications, Nature, vol. 14(1), pages 1-7, December.
    13. 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.
    14. Liming Zheng & Jie Xu & Weihua Wang & Xiaoyin Gao & Chao Zhao & Weijun Guo & Luzhao Sun & Hang Cheng & Fanhao Meng & Buhang Chen & Weiyu Sun & Xia Jia & Xiong Zhou & Kai Wu & Zhongfan Liu & Feng Ding , 2024. "Self-assembled superstructure alleviates air-water interface effect in cryo-EM," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    15. Inbal Maniv & Mahasen Sarji & Anwar Bdarneh & Alona Feldman & Roi Ankawa & Elle Koren & Inbar Magid-Gold & Noa Reis & Despina Soteriou & Shiran Salomon-Zimri & Tali Lavy & Ellina Kesselman & Naama Koi, 2023. "Altered ubiquitin signaling induces Alzheimer’s disease-like hallmarks in a three-dimensional human neural cell culture model," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    16. Benjamin C. Creekmore & Kathryn Kixmoeller & Ben E. Black & Edward B. Lee & Yi-Wei Chang, 2024. "Ultrastructure of human brain tissue vitrified from autopsy revealed by cryo-ET with cryo-plasma FIB milling," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    17. Nathalie Kyalu Ngoie Zola & Clémence Balty & Sébastien Pyr dit Ruys & Axelle A. T. Vanparys & Nicolas D. G. Huyghe & Gaëtan Herinckx & Manuel Johanns & Emilien Boyer & Pascal Kienlen-Campard & Mark H., 2023. "Specific post-translational modifications of soluble tau protein distinguishes Alzheimer’s disease and primary tauopathies," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    18. Peter Kunach & Jaime Vaquer-Alicea & Matthew S. Smith & Jim Monistrol & Robert Hopewell & Luc Moquin & Joseph Therriault & Cecile Tissot & Nesrine Rahmouni & Gassan Massarweh & Jean-Paul Soucy & Marie, 2024. "Cryo-EM structure of Alzheimer’s disease tau filaments with PET ligand MK-6240," Nature Communications, Nature, vol. 15(1), pages 1-7, December.
    19. Iskander Khusainov & Natalie Romanov & Camille Goemans & Beata Turoňová & Christian E. Zimmerli & Sonja Welsch & Julian D. Langer & Athanasios Typas & Martin Beck, 2024. "Bactericidal effect of tetracycline in E. coli strain ED1a may be associated with ribosome dysfunction," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    20. Jinjian Hu & Wencheng Xia & Shuyi Zeng & Yeh-Jun Lim & Youqi Tao & Yunpeng Sun & Lang Zhao & Haosen Wang & Weidong Le & Dan Li & Shengnan Zhang & Cong Liu & Yan-Mei Li, 2024. "Phosphorylation and O-GlcNAcylation at the same α-synuclein site generate distinct fibril structures," Nature Communications, Nature, vol. 15(1), pages 1-13, 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_s41467-024-50686-2. 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.