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Protein Transport and Qualty Control

We study molecular mechanisms of protein targeting to organelles and related quality control pathways using biochemical and structural approaches

Many proteins move across cellular membranes during or soon after synthesis by ribosomes. In eukaryotes, more than one third of proteins are targeted to organelles, such as endoplasmic reticulum (ER), peroxisomes, mitochondria, and plastids, and translocated by protein-conducting channels or protein translocases. Protein translocation poses many fundamental biological questions, such as how channels selectively recognize their substrate proteins, how they translocate large polypeptides while maintaining the membrane barrier for small molecules and ions, and how they enable directional polypeptide movement. In addition to forward translocation, the channels and translocases also work together with protein quality control machineries to ensure proper targeting of proteins. However, the molecular mechanisms of these processes are poorly understood.

We aim to answer these important questions by a combination of structural, biochemical, and biophysical approaches. In particular, we are actively using cryo-electron microscopy (cryo-EM) to elucidate high-resolution structures of these molecular machines in various functional states.

 

Current Research Topics

Click image below for details

Mechanism of the Sec complex

Endoplasmic Reticulum Protein Translocation

Structure of the TOM complex

Mitochondrial Protein Import

Structure of an ER protein quality control factor

ER Protein Quality Control

Recent Publications

  • ∗Wu, K., ∗Itskanov, S., Lynch, D.L., Turner, A., Gumbart, J.C., and †Park, E. (2024). Substrate recognition mechanism of the endoplasmic reticulum-associated ubiquitin ligase Doa10. Nature Communications. 15(1):2182. [Journal link] [bioRxiv]
  • ∗Sim, S.I., ∗Chen, Y., Lynch, D.L., Gumbart, J.C., and †Park, E. (2023). Structural basis of mitochondrial protein import by the TIM23 complex. Nature. 621(7979):620-626. [Journal link] [bioRxiv]
  • ∗Itskanov, S., ∗Wang, L., Junne, T., Sherriff, R., Xiao, L., Blanchard, N., Shi, W.Q., Forsyth, C., Hoepfner, D., Spiess, M., and †Park, E. (2023). A common mechanism of Sec61 translocon inhibition by small molecules. Nature Chemical Biology. Published online on May 11, 2023. [Journal link] [bioRxiv]
  • Sim, S.I., von Bülow, S., Hummer, G., and †Park, E. (2021). Structural basis of polyamine transport by human ATP13A2 (PARK9). Molecular Cell. 81(22):4635-4635. [Journal link] [bioRxiv]
  • Itskanov, S., Kuo, K.M., Gumbart, J.C., and †Park, E. (2021). Stepwise gating of the Sec61 protein-conducting channel by Sec63 and Sec62. Nature Structural & Molecular Biology. 28:162-172. [Journal link] [bioRxiv] [PMC]
  • ∗McKenna, M.J., ∗Sim, S.I., Ordureau, A., Wei, L., Harper J.W., †Shao, S., and †Park, E. (2020). The endoplasmic reticulum P5A-ATPase is a transmembrane helix dislocase. Science. 369(6511):eabc5809. [Journal link] [PMC]

Our Team

Current Lab Members

Photo of Eunyong Park

Eunyong Park, Ph.D.

Principal Investigator; Associate Professor

Eunyong received PhD from Harvard and postdoc training at Rockefeller University. He was awarded Vallee scholarship (2018), Pew Biomedical Scholarship (2020), and Amgen Young Investigator Award (2023).

Photo of Yuanyuan Chen

Yuanyuan Chen, Ph.D.

Postdoc scholar

Yuanyuan received BS and MS in Biochemistry from Nanjing University, and PhD in Chemistry from Ohio State University training with Prof. Ross Dalbey. Yuanyuan joined the lab in Fall 2019.

Photo of Kyungjin Min

Kyungjin Min, Ph.D.

Postdoc scholar

Kyungjin received her BS from UT Austin and PhD in Chemistry from Seoul National University. Kyungjin joined the lab in 2020 and received a Korean NRF followship.

Photo of Kevin Wu

Kevin Wu, Ph.D.

Postdoc fellow

Kevin received BS/MS from National Taiwan Univ., and PhD in Biophysics from U. Michigan with Prof. Jim Bardwell. Kevin joined the lab in 2022 and awarded a Jane Coffin Childs fellowship

Photo of Laurie Wang

Laurie Wang

Ph.D. candidate

Laurie received her BS from Yale. After working at a pharmaceutical company for two years, she joined the MCB PhD Program in 2021. Laurie joined the lab in 2022 and received an NSF fellowship.

Photo of Nate Dempsey

Nate Dempsey

Ph.D. candidate

Nate received his AB in Molecular and Cellular Biology from Harvard in 2020. Nate entered the MCB PhD program in 2022 as a Berkeley Fellow and joined the lab in 2023.

Photo of Sam Garcia

Samantha Garcia

Ph.D. candidate

Sam received her BS in Cellular & Molecular Biochemistry from the UT El Paso in 2022. She entered the MCB PhD program in 2022 and joined the lab in 2023.

Photo of Amy Jung

Amy Jung

Ph.D. student

Amy received her BA in Molecular and Cell Biology from UC Berkeley in 2022. She entered the PhD program in 2022 and joined the lab in Fall 2023.

Photo of Carson Gido

Carson Gido

Ph.D. student

Carson received his BS in Biochemistry from Kansas State University in 2023. He entered the Biophysics PhD program in 2023 and joined the lab in 2024.

Alumni

Jessica Cope, undergraduate student, 2023-2024 (currently postbac at OHSU)
Aasha Turner, undergraduate student, 2023-2024 (currently postbac at Dana-Farber)
Jacob Spiegel, undergraduate student, 2024
Sue Sim, Ph.D. student, 2019-2023 (currently postdoc at UCSF)
Samuel Itskanov, Ph.D. student, 2018-2022 (currently postdoc at Gilead)
Phanisri Tummala, undergraduate student, 2021-2022 (currently medical school student)
Nicholas Sims, undergraduate student, 2022
Ivan Savchuk, undergraduate student, 2021
Kyle Tucker, graduate student, 2018-2020
Miaomiao Chen, undergraduate exchange student, 2018 (thereafter, Ph.D. at UVA)

About the lab

Group photo in 2023

Group Photo in 2023

Our lab started in 2018 in the Department of Molecular and Cell Biolgy (MCB) at UC Berkeley. We are a highly motived group of scientists from diverse backgrounds and love to engage with challenging problems in cell biology and make new discoveries. We use biochemical, structural (cryo-EM), and cell biology tools elucidate molecular mechanisms related to protein transport across organellar membranes and quality control.

Our laboratory is located in Stanley Hall of UC Berkeley, the home of QB3 Berkeley. Founded in 1868, UC Berkeley has been on the frontier of science and engineering research. It ranks as one of top public universities in the world. Stanley Hall serves as the Berkeley hub for multidisciplinary research and teaching involving the biological sciences, physical sciences, and engineering. Built in 2007, Stanley Hall houses 40 research laboratories for QB3 faculty affiliates and several support facilities including Berkeley Bay Area Cryo-EM facility (operating FEI Titan Krios and Talos Arctica microscopes)

Join Us

We have open positions for postdoctoral scholars who are interested in biology of organelle biogenesis, protein targeting, and quality control. Prior training in protein biochemistry, cell biology, or biophysics is desirable. Projects will use yeast and/or mammalian cells as model systems and a combination of biochemical, cell biology (light microscopy), and, potentially, cryo-EM methods (no prior training in cryo-EM is required). Applicants are expected to have at least one peer-reviewed first-author paper to demonstrate their research proficiency. Interested applicants should submit CV and cover letter to eunyong_park(at) berkeley.edu .

We accept graduate students through the MCB and Biophysics programs. If you are a first-year MCB or Biophysics student and interested in rotation, please contact Professor Eunyong Park to set up a meeting.

 


Our research sponsors

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Logo of Pew Charitable Trust

Park lab

Department of Molecular and Cell Biology

University of California, Berkeley