Faculty & Research
Jungsan (Jay) Sohn
Biophysics & Biophysical Chemistry|
|Phone Numbers||(401) 287-1957|
Fax: (410) 5026910
|School of Medicine Address||725 N. Wolfe St. |
Baltimore MD 21205
|Link to Lab Homepage|
Research Topic: We are interested in understanding how biological stress-sensors are assembled, detect danger signals, and initiate stress-response.
Structural Mechanistic Biochemistry. Innate immunity is the first line of defense against invading pathogens in higher eukaryotes. The central players of this well-conserved form of immune response are pattern-recognition receptors (PRRs) that can recognize pathogen associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs). NOD-like receptors (NLRs) are important PRRs of innate immunity. Notably, upon binding PAMP/DAMP and nucleoside-triphosphates (NTP), NLRs assemble into multi-protein complexes called inflammasomes.The assembled inflammasomes thentransduce upstream signals to directly activate inflammatory kinases and/or caspases. The activated inflammatory enzymes such as RIP-2 kinase (RIPK2) and caspase-1 then facilitate production and maturation of inflammatory cytokines such as Interleukin 1-b (IL-1b), respectively (Fig. 1).
NLRs often play important roles in coping with bacterial and viral infections. Moreover, autoimmune disorders (e.g., Crohn’s disease, gout, rheumatoid arthritis, and vitiligo), neurodegenerative diseases (e.g., cerebral ischemia and Alzheimer’s disease), and several forms of cancer (e.g., melanoma and lung cancer) are closely associated with NLR malfunctions. Despite the well-established biological significance and implications in human health, the current understanding of the molecular mechanism of inflammasomes is quite poor.
We are using in vitro quantitative biochemical assays and mutagenesis, and x-ray crystallography to investigate the underlying operating principles of these machines. Understanding the structural and functional mechanisms of inflammasomes will address important questions concerning innate immunity and will also help designing small molecule modulators of function in vivo. We are specifically interested in asking following questions:
- What is the mechanism of inflammasome assembly?
- What is the mechanism of target-protein activation by inflammasomes?
- What are the molecular mechanisms of inflammasome regulation by protein modulators
Sohn J, Grant RA, Sauer RT. (2010) Allostery is an intrinsic property of the protease domain of DegS: implications for enzyme function and evolution J. Biol. Chem. 285, 34039-47.
Sohn J, Grant RA. Sauer RT. (2009) OMP peptides activate the DegS protease by a relief of inhibition mechanism. Structure 17:1411-21.
Sohn J. and Saue, RT. (2009) OMP peptides modulate the activity of DegS protease by differential binding to active and inactive conformations. Molecular Cell 33, 64-74.
, Grant RA, Sauer RT. (2007) Allosteric activation of DegS, a stress sensor PDZ-protease. Cell 131
, 572-583.PubMed Reference