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Structural insights into E1 recognition and the ubiquitin-conjugating activity of the E2 enzyme Cdc34

Author

Listed:
  • Katelyn M. Williams

    (Medical University of South Carolina)

  • Shuo Qie

    (Medical University of South Carolina)

  • James H. Atkison

    (Medical University of South Carolina)

  • Sabrina Salazar-Arango

    (Medical University of South Carolina)

  • J. Alan Diehl

    (Medical University of South Carolina)

  • Shaun K. Olsen

    (Medical University of South Carolina)

Abstract

Ubiquitin (Ub) signaling requires the sequential interactions and activities of three enzymes, E1, E2, and E3. Cdc34 is an E2 that plays a key role in regulating cell cycle progression and requires unique structural elements to function. The molecular basis by which Cdc34 engages its E1 and the structural mechanisms by which its unique C-terminal extension functions in Cdc34 activity are unknown. Here, we present crystal structures of Cdc34 alone and in complex with E1, and a Cdc34~Ub thioester mimetic that represents the product of Uba1-Cdc34 Ub transthiolation. These structures reveal conformational changes in Uba1 and Cdc34 and a unique binding mode that are required for transthiolation. The Cdc34~Ub structure reveals contacts between the Cdc34 C-terminal extension and Ub that stabilize Cdc34~Ub in a closed conformation and are critical for Ub discharge. Altogether, our structural, biochemical, and cell-based studies provide insights into the molecular mechanisms by which Cdc34 function in cells.

Suggested Citation

  • Katelyn M. Williams & Shuo Qie & James H. Atkison & Sabrina Salazar-Arango & J. Alan Diehl & Shaun K. Olsen, 2019. "Structural insights into E1 recognition and the ubiquitin-conjugating activity of the E2 enzyme Cdc34," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11061-8
    DOI: 10.1038/s41467-019-11061-8
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    Cited by:

    1. Iona Wallace & Kheewoong Baek & J. Rajan Prabu & Ronnald Vollrath & Susanne Gronau & Brenda A. Schulman & Kirby N. Swatek, 2023. "Insights into the ISG15 transfer cascade by the UBE1L activating enzyme," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    2. Mohammad Afsar & GuanQun Liu & Lijia Jia & Eliza A. Ruben & Digant Nayak & Zuberwasim Sayyad & Priscila dos Santos Bury & Kristin E. Cano & Anindita Nayak & Xiang Ru Zhao & Ankita Shukla & Patrick Sun, 2023. "Cryo-EM structures of Uba7 reveal the molecular basis for ISG15 activation and E1-E2 thioester transfer," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    3. Lingmin Yuan & Fei Gao & Zongyang Lv & Digant Nayak & Anindita Nayak & Priscila dos Santos Bury & Kristin E. Cano & Lijia Jia & Natalia Oleinik & Firdevs Cansu Atilgan & Besim Ogretmen & Katelyn M. Wi, 2022. "Crystal structures reveal catalytic and regulatory mechanisms of the dual-specificity ubiquitin/FAT10 E1 enzyme Uba6," Nature Communications, Nature, vol. 13(1), pages 1-14, December.

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