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Cryo-EM reveals structural basis for human AIM/CD5L recognition of polymeric immunoglobulin M

Author

Listed:
  • Qu Chen

    (The Francis Crick Institute)

  • Kazuhiro Ishii

    (The Institute for AIM Medicine
    The University of Tokyo)

  • Haruka Mori

    (The Institute for AIM Medicine)

  • Akemi Nishijima

    (The Institute for AIM Medicine)

  • Satoko Arai

    (The Institute for AIM Medicine)

  • Toru Miyazaki

    (The Institute for AIM Medicine
    Japan Agency for Medical Research and Development
    Université de Strasbourg)

  • Peter B. Rosenthal

    (The Francis Crick Institute)

Abstract

Cell surface scavenger receptors contribute to homoeostasis and the response to pathogens and products associated with damage by binding to common molecular features on a wide range of targets. Apoptosis inhibitor of macrophage (AIM/CD5L) is a soluble protein belonging to the scavenger receptor cysteine-rich (SRCR) superfamily that contributes to prevention of a wide range of diseases associated with infection, inflammation, and cancer. AIM forms complexes with IgM pentamers which helps maintain high-levels of circulating AIM in serum for subsequent activation on release from the complex. The structural basis for AIM recognition of IgM as well as other binding targets is unknown. Here we apply cryogenic electron microscopy imaging (cryo-EM) to show how interfaces on both of AIM’s C-terminal SRCR domains interact with the Fcμ constant region and J chain components of the IgM core. Both SRCR interfaces are also shown to contribute interactions important for AIM binding to damage-associated molecular patterns (DAMPs).

Suggested Citation

  • Qu Chen & Kazuhiro Ishii & Haruka Mori & Akemi Nishijima & Satoko Arai & Toru Miyazaki & Peter B. Rosenthal, 2024. "Cryo-EM reveals structural basis for human AIM/CD5L recognition of polymeric immunoglobulin M," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53615-5
    DOI: 10.1038/s41467-024-53615-5
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