Assistant Professor of Biochemistry
B.S. Brigham Young University
Ph.D. Brigham Young University
Peter Shen's Lab Page
Peter Shen's PubMed Literature Search
Molecular Biology Program
Biological Chemistry Program
Protein quality control, proteopathy, protein complexes, cryo-EM
Protein quality control
Protein homeostasis is critical to maintaining a healthy cellular environment. All proteins rely on quality control mechanisms to ensure proper synthesis, folding, function, and turnover. Dysregulation along these pathways contribute to some of the most devastating diseases in humans, including neurodegeneration. My lab seeks to resolve the molecular mechanisms that are responsible for ensuring proper protein quality control. The mechanisms that we uncover will become the basis of developing therapeutics to rescue quality control failure.
My lab studies one of the central players in regulating eukaryotic protein homeostasis: the AAA+ Cdc48/p97 complex. Cdc48 is best characterized for its role in targeting ubiquitinated substrates for proteasomal degradation. It is a highly abundant protein and its regulation is mediated by dozens of co-factors. How these co-factors drive Cdc48 function and regulation is an open mystery and my lab will develop the tools to purify, visualize, and characterize these complexes.
Seeing is Believing
My lab specializes in cryo-EM to resolve 3D structures at atomic resolution. Cryo-EM is uniquely suited for working with structurally heterogeneous samples because a single sample often reveals a range of structural states that can then be pieced together to deduce mechanism and dynamics. The ability to directly visualize these biological molecules will enable us to understand how multiple components come together to carry out their evolutionarily tuned functions.
- Monroe N, Han H, Shen PS*, Sundquist WI*, Hill CP*. Structural Basis of Protein Translocation by the Vps4-Vta1 AAA ATPase. Elife. 2017 Apr 5;6. (*co-corresponding author)
- Shen PS*, Yang X*, DeCaen PG, Liu X, Bulkley D, Clapham DE, Cao E. The Structure of Polycystic Kidney Disease Channel PKD2 in Lipid Nanodiscs. Cell. 2016 Oct 20:167(3):763-73
- Shen PS, Park J, Qin Y, Parsawar K, Li X, Larson M, Cox J, Cheng Y, Lambowitz AM, Weissman
JS, Brandman O, Frost A. Rqc2p and the 60S ribosome mediate mRNA-independent elongation of nascent chains. Science. 2015 Jan 2;347(6217):75-8
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- Brandman O, Stewart-Ornstein J, Wong D, Larson A, Williams CC, Li GW, Zhou S, King D, Shen PS, Weibezahn J, Dunn JG, Rouskin S, Inada T, Frost A, Weissman JS. A ribosome-bound quality control complex triggers degradation of nascent peptides and signals translation stress. Cell. 2012 Nov 21;151(5):1042-54.