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Subtleties in Clathrin heavy chain binding boxes provide selectivity among adaptor proteins of budding yeast

Author

Listed:
  • Lucas A. Defelipe

    (European Molecular Biology Laboratory - Hamburg Unit
    Centre for Structural Systems Biology)

  • Katharina Veith

    (European Molecular Biology Laboratory - Hamburg Unit
    Centre for Structural Systems Biology)

  • Osvaldo Burastero

    (European Molecular Biology Laboratory - Hamburg Unit
    Centre for Structural Systems Biology)

  • Tatiana Kupriianova

    (European Molecular Biology Laboratory - Hamburg Unit
    Centre for Structural Systems Biology)

  • Isabel Bento

    (European Molecular Biology Laboratory - Hamburg Unit)

  • Michal Skruzny

    (European Molecular Biology Laboratory
    Max Planck Institute for Terrestrial Microbiology
    Carl Zeiss Microscopy GmbH)

  • Knut Kölbel

    (Centre for Structural Systems Biology
    Leibniz Institute of Virology (LIV)
    Deutsches Elektronen Synchrotron - DESY)

  • Charlotte Uetrecht

    (Centre for Structural Systems Biology
    Leibniz Institute of Virology (LIV)
    Deutsches Elektronen Synchrotron - DESY
    University of Lübeck)

  • Roland Thuenauer

    (Centre for Structural Systems Biology
    Leibniz Institute of Virology (LIV)
    Universität Hamburg (UHH))

  • Maria M. García-Alai

    (European Molecular Biology Laboratory - Hamburg Unit
    Centre for Structural Systems Biology)

Abstract

Clathrin forms a triskelion, or three-legged, network that regulates cellular processes by facilitating cargo internalization and trafficking in eukaryotes. Its N-terminal domain is crucial for interacting with adaptor proteins, which link clathrin to the membrane and engage with specific cargo. The N-terminal domain contains up to four adaptor-binding sites, though their role in preferential occupancy by adaptor proteins remains unclear. In this study, we examine the binding hierarchy of adaptors for clathrin, using integrative biophysical and structural approaches, along with in vivo functional experiments. We find that yeast epsin Ent5 has the highest affinity for clathrin, highlighting its key role in cellular trafficking. Epsins Ent1 and Ent2, crucial for endocytosis but thought to have redundant functions, show distinct binding patterns. Ent1 exhibits stronger interactions with clathrin than Ent2, suggesting a functional divergence toward actin binding. These results offer molecular insights into adaptor protein selectivity, suggesting they competitively bind clathrin while also targeting three different clathrin sites.

Suggested Citation

  • Lucas A. Defelipe & Katharina Veith & Osvaldo Burastero & Tatiana Kupriianova & Isabel Bento & Michal Skruzny & Knut Kölbel & Charlotte Uetrecht & Roland Thuenauer & Maria M. García-Alai, 2024. "Subtleties in Clathrin heavy chain binding boxes provide selectivity among adaptor proteins of budding yeast," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-54037-z
    DOI: 10.1038/s41467-024-54037-z
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    References listed on IDEAS

    as
    1. Javier Lizarrondo & David P. Klebl & Stephan Niebling & Marc Abella & Martin A. Schroer & Haydyn D. T. Mertens & Katharina Veith & Roland Thuenauer & Dmitri I. Svergun & Michal Skruzny & Frank Sobott , 2021. "Structure of the endocytic adaptor complex reveals the basis for efficient membrane anchoring during clathrin-mediated endocytosis," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    2. Maria M. Garcia-Alai & Johannes Heidemann & Michal Skruzny & Anna Gieras & Haydyn D. T. Mertens & Dmitri I. Svergun & Marko Kaksonen & Charlotte Uetrecht & Rob Meijers, 2018. "Epsin and Sla2 form assemblies through phospholipid interfaces," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
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