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Structure and dynamics of the ASB9 CUL-RING E3 Ligase

Author

Listed:
  • Ryan J. Lumpkin

    (University of California, San Diego)

  • Richard W. Baker

    (University of California, San Diego
    University of North Carolina, Chapel Hill
    University of North Carolina, Chapel Hill)

  • Andres E. Leschziner

    (University of California, San Diego
    University of California, San Diego)

  • Elizabeth A. Komives

    (University of California, San Diego)

Abstract

The Cullin 5 (CUL5) Ring E3 ligase uses adaptors Elongins B and C (ELOB/C) to bind different SOCS-box-containing substrate receptors, determining the substrate specificity of the ligase. The 18-member ankyrin and SOCS box (ASB) family is the largest substrate receptor family. Here we report cryo-EM data for the substrate, creatine kinase (CKB) bound to ASB9-ELOB/C, and for full-length CUL5 bound to the RING protein, RBX2, which binds various E2s. To date, no full structures are available either for a substrate-bound ASB nor for CUL5. Hydrogen–deuterium exchange (HDX-MS) mapped onto a full structural model of the ligase revealed long-range allostery extending from the substrate through CUL5. We propose a revised allosteric mechanism for how CUL-E3 ligases function. ASB9 and CUL5 behave as rigid rods, connected through a hinge provided by ELOB/C transmitting long-range allosteric crosstalk from the substrate through CUL5 to the RBX2 flexible linker.

Suggested Citation

  • Ryan J. Lumpkin & Richard W. Baker & Andres E. Leschziner & Elizabeth A. Komives, 2020. "Structure and dynamics of the ASB9 CUL-RING E3 Ligase," Nature Communications, Nature, vol. 11(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16499-9
    DOI: 10.1038/s41467-020-16499-9
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