IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-32577-6.html
   My bibliography  Save this article

Structure of the human NK cell NKR-P1:LLT1 receptor:ligand complex reveals clustering in the immune synapse

Author

Listed:
  • Jan Bláha

    (Charles University
    EMBL, Hamburg Unit c/o DESY)

  • Tereza Skálová

    (BIOCEV Centre)

  • Barbora Kalousková

    (Charles University
    Institute of Applied Physics – Biophysics group, TU Wien)

  • Ondřej Skořepa

    (Charles University)

  • Denis Cmunt

    (Charles University
    University of Lausanne)

  • Valéria Grobárová

    (Charles University)

  • Samuel Pazicky

    (Charles University
    Nanyang Technological University)

  • Edita Poláchová

    (Charles University)

  • Celeste Abreu

    (Charles University)

  • Jan Stránský

    (BIOCEV Centre)

  • Tomáš Kovaľ

    (BIOCEV Centre)

  • Jarmila Dušková

    (BIOCEV Centre)

  • Yuguang Zhao

    (University of Oxford)

  • Karl Harlos

    (University of Oxford)

  • Jindřich Hašek

    (BIOCEV Centre)

  • Jan Dohnálek

    (BIOCEV Centre)

  • Ondřej Vaněk

    (Charles University)

Abstract

Signaling by the human C-type lectin-like receptor, natural killer (NK) cell inhibitory receptor NKR-P1, has a critical role in many immune-related diseases and cancer. C-type lectin-like receptors have weak affinities to their ligands; therefore, setting up a comprehensive model of NKR-P1-LLT1 interactions that considers the natural state of the receptor on the cell surface is necessary to understand its functions. Here we report the crystal structures of the NKR-P1 and NKR-P1:LLT1 complexes, which provides evidence that NKR-P1 forms homodimers in an unexpected arrangement to enable LLT1 binding in two modes, bridging two LLT1 molecules. These interaction clusters are suggestive of an inhibitory immune synapse. By observing the formation of these clusters in solution using SEC-SAXS analysis, by dSTORM super-resolution microscopy on the cell surface, and by following their role in receptor signaling with freshly isolated NK cells, we show that only the ligation of both LLT1 binding interfaces leads to effective NKR-P1 inhibitory signaling. In summary, our findings collectively support a model of NKR-P1:LLT1 clustering, which allows the interacting proteins to overcome weak ligand-receptor affinity and to trigger signal transduction upon cellular contact in the immune synapse.

Suggested Citation

  • Jan Bláha & Tereza Skálová & Barbora Kalousková & Ondřej Skořepa & Denis Cmunt & Valéria Grobárová & Samuel Pazicky & Edita Poláchová & Celeste Abreu & Jan Stránský & Tomáš Kovaľ & Jarmila Dušková & Y, 2022. "Structure of the human NK cell NKR-P1:LLT1 receptor:ligand complex reveals clustering in the immune synapse," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32577-6
    DOI: 10.1038/s41467-022-32577-6
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-32577-6
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-022-32577-6?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. Gautham R. Balaji & Oscar A. Aguilar & Miho Tanaka & Miguel A. Shingu-Vazquez & Zhihui Fu & Benjamin S. Gully & Lewis L. Lanier & James R. Carlyle & Jamie Rossjohn & Richard Berry, 2018. "Recognition of host Clr-b by the inhibitory NKR-P1B receptor provides a basis for missing-self recognition," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    2. Carin C. Stamper & Yan Zhang & James F. Tobin & David V. Erbe & Shinji Ikemizu & Simon J. Davis & Mark L. Stahl & Jasbir Seehra & William S. Somers & Lidia Mosyak, 2001. "Crystal structure of the B7-1/CTLA-4 complex that inhibits human immune responses," Nature, Nature, vol. 410(6828), pages 608-611, March.
    3. Jean-Claude D. Schwartz & Xuewu Zhang & Alexander A. Fedorov & Stanley G. Nathenson & Steven C. Almo, 2001. "Structural basis for co-stimulation by the human CTLA-4/B7-2 complex," Nature, Nature, vol. 410(6828), pages 604-608, March.
    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. Chuanyuan Wei & Wei Sun & Kangjie Shen & Jingqin Zhong & Wanlin Liu & Zixu Gao & Yu Xu & Lu Wang & Tu Hu & Ming Ren & Yinlam Li & Yu Zhu & Shaoluan Zheng & Ming Zhu & Rongkui Luo & Yanwen Yang & Yingy, 2023. "Delineating the early dissemination mechanisms of acral melanoma by integrating single-cell and spatial transcriptomic analyses," Nature Communications, Nature, vol. 14(1), pages 1-20, 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. Shangyu Yang & Yong Wang & Feiyang Yu & Rao Cheng & Yiwei Zhang & Dan Zhou & Xuanxiu Ren & Zengqin Deng & Haiyan Zhao, 2023. "Structural and functional insights into the modulation of T cell costimulation by monkeypox virus protein M2," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    2. Michal Scur & Ahmad Bakur Mahmoud & Sayanti Dey & Farah Abdalbarri & Iona Stylianides & Daniel Medina-Luna & Gayani S. Gamage & Aaron Woblistin & Alexa N. M. Wilson & Haggag S. Zein & Ashley Stueck & , 2022. "Alveolar macrophage metabolic programming via a C-type lectin receptor protects against lipo-toxicity and cell death," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    3. Mark F. Maurer & Katherine E. Lewis & Joseph L. Kuijper & Dan Ardourel & Chelsea J. Gudgeon & Siddarth Chandrasekaran & Sherri L. Mudri & Kayla N. Kleist & Chris Navas & Martin F. Wolfson & Mark W. Ri, 2022. "The engineered CD80 variant fusion therapeutic davoceticept combines checkpoint antagonism with conditional CD28 costimulation for anti-tumor immunity," Nature Communications, Nature, vol. 13(1), pages 1-14, 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:13:y:2022:i:1:d:10.1038_s41467-022-32577-6. 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.