Biochemistry and biophysics PhD student, Cathy Spangler, researches in Robert McGinty’s lab and recently published a paper in collaboration with Joshua Boyer, Joshua Strauss, Andrew Cesmat, Pengda Liu, Robert McGinty, and Qi Zhang, titled Structural basis of nucleosome-dependent cGAS inhibition. This article addresses the use of cryo-electron microscopy to determine the high-resolution structure of a DNA-sensing protein called cGAS bound to the nucleosome – the fundamental repeating unit of chromatin. A key sensor in our body’s innate immune system, cGAS detects foreign or damaged DNA and triggers the body’s response against infected or cancerous cells. This work reveals molecular details about how the nucleosome binds to cGAS and inhibits it from mistakenly triggering an autoimmune response to our own healthy DNA. Cathy’s research aims to visualize key protein interactions in the nucleus at near-atomic resolution. Many of these proteins, such as cGAS, are dysfunctional in cancers and autoimmune diseases. Discovering the structural details about how these proteins function helps researchers identify new strategies for drug development.
This paper was published online by the journal Science in September 2020. DOI: 10.1126/science.abd0609