Professional Education

  • Doctor of Philosophy, University of California San Francisco (2020)
  • Bachelor of Arts, Colby College, Chemistry (2011)
  • BA, Colby College, Chemistry (2011)
  • PhD, University of California, San Francisco, Chemical Biology (2020)

Stanford Advisors

Contact

  • Academic
    kaopokun@stanford.edu
    University - Scholar Department: Biology Position: Postdoctoral Scholar

Additional Info

All Publications

  • A structural vista of phosducin-like PhLP2A-chaperonin TRiC cooperation during the ATP-driven folding cycle. Nature communications Park, J., Kim, H., Gestaut, D., Lim, S., Opoku-Nsiah, K. A., Leitner, A., Frydman, J., Roh, S. 2024; 15 (1): 1007

    Abstract

    Proper cellular proteostasis, essential for viability, requires a network of chaperones and cochaperones. ATP-dependent chaperonin TRiC/CCT partners with cochaperones prefoldin (PFD) and phosducin-like proteins (PhLPs) to facilitate folding of essential eukaryotic proteins. Using cryoEM and biochemical analyses, we determine the ATP-driven cycle of TRiC-PFD-PhLP2A interaction. PhLP2A binds to open apo-TRiC through polyvalent domain-specific contacts with its chamber's equatorial and apical regions. PhLP2A N-terminal H3-domain binding to subunits CCT3/4 apical domains displace PFD from TRiC. ATP-induced TRiC closure rearranges the contacts of PhLP2A domains within the closed chamber. In the presence of substrate, actin and PhLP2A segregate into opposing chambers, each binding to positively charged inner surface residues from CCT1/3/6/8. Notably, actin induces a conformational change in PhLP2A, causing its N-terminal helices to extend across the inter-ring interface to directly contact a hydrophobic groove in actin. Our findings reveal an ATP-driven PhLP2A structural rearrangement cycle within the TRiC chamber to facilitate folding.

    View details for DOI 10.1038/s41467-024-45242-x

    View details for PubMedID 38307855

  • The YPhi motif defines the structure-activity relationships of human 20S proteasome activators. Nature communications Opoku-Nsiah, K. A., de la Pena, A. H., Williams, S. K., Chopra, N., Sali, A., Lander, G. C., Gestwicki, J. E. 2022; 13 (1): 1226

    Abstract

    The 20S proteasome (20S) facilitates turnover of most eukaryotic proteins. Substrate entry into the 20S first requires opening of gating loops through binding of HbYX motifs that are present at the C-termini of certain proteasome activators (PAs). The HbYX motif has been predominantly characterized in the archaeal 20S, whereas little is known about the sequence preferences of the human 20S (h20S). Here, we synthesize and screen ~120 HbYX-like peptides, revealing unexpected differences from the archaeal system and defining the h20S recognition sequence as the Y-F/Y (YФ) motif. To gain further insight, we create a functional chimera of the optimized sequence, NLSYYT, fused to the model activator, PA26E102A. A cryo-EM structure of PA26E102A-h20S is used to identify key interactions, including non-canonical contacts and gate-opening mechanisms. Finally, we demonstrate that the YФ sequence preferences are tuned by valency, allowing multivalent PAs to sample greater sequence space. These results expand the model for termini-mediated gating and provide a template for the design of h20S activators.

    View details for DOI 10.1038/s41467-022-28864-x

    View details for PubMedID 35264557

https://orcid.org/0000-0002-4059-9746