Departments & Divisions
Institutes and Centers
Department of Biochemistry & Structural Biology
Currently seeking Ph.D. students.
In broad terms, the research in my laboratory focuses on mechanisms of molecular recognition in protein-protein interactions and on the structural enzymology of proteins essential for cellular function. The majority of our efforts are focused on understanding how enzymes in the ubiquitin (Ub) conjugation cascade (E1, E2, and E3) function together to conjugate Ub to cellular proteins. Post-translational modification of proteins by Ub is a means of regulating fundamental cellular processes including cell cycle control, DNA repair, signal transduction, and immunity. The importance of understanding how the Ub system works is underscored by the fact that dysregulation of Ub signaling is implicated in a number of human disorders and that the pathway is a validated target for therapeutic intervention in cancer. To achieve our goals, we employ a multidisciplinary approach that includes X-ray crystallography, single particle cryo-EM, enzymology, and a variety of biochemical and biophysical techniques. When appropriate, we use yeast genetics and eukaryotic cell-based functional assays to assess the biological importance of our structural, biochemical, and biophysical findings. We are also involved in collaborative studies with our colleagues at the CPRIT-supported Center for Innovative Drug Discovery (CIDD) to identify small molecule inhibitors of enzymes and PROTACs targeting enzymes involved in Ub signaling and DNA repair.
Structural biology of signaling by ubiquitin and ubiquitin-like proteins.
1R01GM115568: Olsen (PI); 9/1/2020– 8/31/2024; Structural Biology of the Ubiquitin Conjugation System
1R01GM128731: Olsen (PI); 4/15/2019– 2/28/2023; Structure and function of the essential cell cycle regulator Cdc34
Olsen SK, Capili AD, Lu X, Tan DS, Lima CD. (2010) Active site remodelling accompanies thioester bond formation in the SUMO E1. Nature Feb 18;463(7283):906-12
Olsen SK & Lima CD. (2013) Structure of a ubiquitin E1-E2 complex: insights to E1-E2 thioester transfer. Molecular Cell Mar 7;49(5):884-96
Atkison JH, Parnham S, Marcotte WR Jr, Olsen SK. (2016) Crystal Structure of the Nephila clavipes Major Ampullate Spidroin 1A N-terminal Domain Reveals Plasticity at the Dimer Interface. J. Biol. Chem. Sep 2;291(36):19006-17
Lv Z, Rickman KA, Yuan L, Williams K, Selvam SP, Woosley AN, Howe, PH, Ogretmen B, Smogorzewska A, Olsen SK. (2017) S. pombe Uba1-Ubc15 structure reveals a novel regulatory mechanism of ubiquitin E2 activity. Molecular Cell Feb 16; 65(4):699-714
Lv Z, Yuan L, Atkison JH, Aldana-Masangkay G, Chen Y, Olsen SK. (2017) Domain Alternation and Active Site Remodeling Are Conserved Structural Features of Ubiquitin E1. J. Biol. Chem. Jul 21;292(29):12089-12099
Yuan L, Lv Z, Atkison JH, Olsen SK. (2017) Structural insights into the mechanism and E2 specificity of the RBR E3 ubiquitin ligase HHARI. Nature Communications Aug 8;8(1):211
Lv Z, Williams KM, Yuan L, Atkison JH, Olsen SK. (2018). Crystal structure of a human ubiquitin E1-ubiquitin complex reveals conserved functional elements essential for activity. J. Biol. Chem. Nov 23;293(47): 18337-18352
Lv Z, Yuan L, Atkison JH, Williams KM, Vega R, Sessions EH, Divlianska DB, Davies C, Chen Y, Olsen SK. (2018) Molecular mechanism of a covalent allosteric inhibitor of SUMO E1 activating enzyme. Nature Communications Dec 4;9(1)
Lv Z, Olsen SK. (2019) UFM1-Activating Enzyme (Uba5) Requires an Extension to Get the Job Done Right. J. Mol. Biol. Feb 1;431(3):479:482
Williams KM, Qie S, Atkison JH, Salazar-Arango S, Diehl JA, Olsen SK. (2019) Structural insights into E1 recognition and the ubiquitin-conjugating activity of the E2 enzyme Cdc34. Nature Communications Jul 24;10(1):3296
Rut W, Lv Z, Zmudzindki M, Patchett S, Nayak D, Snipas SJ, El Oualid F, Huang TT, Bekes M, Drag M, Olsen SK. (2020) Activity profiling and structures of inhibitor-bound SARS-CoV-2-PLpro protease provides a framework for anti-COVID-19 drug design. Science Advances In press