Göttinger Graduiertenzentrum für Neurowissenschaften, Biophysik und Molekulare Biowissenschaften

Sakata, Eri, Ph.D*

Group leader at Institute for Auditory Neuroscience


  • 2004-2007: PhD thesis at Nagoya City University, Japan
  • 2011–2013: Postdoctoral fellow at Yale University, USA
  • 2013–2019: Project Group Leader at Max Planck Institute of Biochemistry, Germany
  • since 2019: Group leader at Institute for Auditory Neuroscience, University Medical Center Göttingen, Germany



Major Research Interests

My group works on the structural biology of the ubiquitin-proteasome system (UPS). The UPS has a fundamental role in protein homeostasis in eukaryotic cells and malfunction of the system leads to multiple diseases such as cancer, neurodegenerative diseases, and auto-immune diseases. We focus on understanding the functional and regulatory mechanisms of AAA+ ATPases in the UPS, such as the 26S proteasome and p97, by cryo-electron microscopy (cryo-EM). We have studied the conformational dynamics and regulatory mechanisms of the 26S proteasome using cryo-EM. We addressed the mechanisms of how the 26S proteasome couples ATP hydrolysis to substrate translocation, and how the proteasome-cofactor Ubp6 leads the proteasome to an inactive conformation to regulate the proteolysis rate. Our studies revealed key elements of intersubunit communication within the proteasome and clarified the regulation of substrate degradation. We are further investigating mechanochemical coupling of the conformational dynamics of the AAA+ ATPases such as 26S proteasome and p97, to ATP hydrolysis. The ubiquitin-proteasome pathway has been the target of extensive drug-design efforts. Our research will provide a structural basis for the regulation of these AAA+ ATPases. We aim to provide an atomic-level insight into their regulatory mechanisms, which could lead to drug discovery.


Homepage Department/Research Group
http://www.auditory-neuroscience.uni-goettingen.de/group_Sakata.html


Selected Recent Publications


  • Sakata E., Eisele M. R., Baumeister W. Molecular and cellular dynamics of the 26S proteasome. Biochim Biophys Acta Proteins Proteom 1869(3): 140583 (2021).

  • Eisele M. R., Reed R. G., Rudack T., Schweitzer A., Beck F., Nagy I., Pfeifer G., Plitzko J. M., Baumeister W., Tomko R. J., Jr., Sakata E. Expanded Coverage of the 26S Proteasome Conformational Land-scape Reveals Mechanisms of Peptidase Gating.
    Cell Rep 24, 1301-1315 (2018)

  • Wehmer M, Rudack T, Beck F, Aufderheide A, Pfeifer G, Plitzko JM, Förster F, Schulten K, Baumeister W*, Sakata E. Structural insights into the functional cycle of the ATPase module of the 26S proteasome. Proc Natl Acad Sci U S A. 114(6):1305-1310 (2017)

  • Sakata E., Bohn, S., Miharache,O., Kiss, P., Beck, F., Nickell S., Tanaka, K., Saeki, Y., Förster F., Baumeister, W. Localization of the proteasomal ubiquitin receptors Rpn10 and Rpn13 by electron cryomicroscopy. Proc. Natl. Acad. Sci. U. S. A., 109, 1479-1484, (2012)

  • Sakata E.*, Stengel, F.*, Fukunaga, K., Zhou, M., Saeki, Y., Förster, F., Tanaka, K., Baumeister, W., and Robinson, C.V. The catalytic activity of Ubp6 enhances maturation of the proteasomal regulatory particle. Mol. Cell, 42, 637-649, (2011)