Researchers from Monash University have made a groundbreaking discovery by solving the structure of a protein called LYCHOS, which can detect and regulate cell growth by sensing cholesterol levels in the body. This finding reveals a surprising connection between human cells and plant-like mechanisms, opening new avenues for targeted drug development to tackle diseases driven by abnormal cell growth, such as cancer and neurological disorders.
The LYCHOS Hybrid
The scientists were surprised and excited to study the results. By cryo-electron microscopy (cryo-EM), they obtained the first 3D structure of LYCHOS, uncovering a distinct chimeric composition of cell transporters similar in plants (but not mammals) and G protein-coupled receptor (GPCR). The unforeseen find contradicts the prevailing notion of human cell biology.
LYCHOS is a cholesterol sensor that switches on the mTORC1 protein complex, which Associate Professor Andrew Ellisdon said is important for the regulation of cell growth and metabolism. LYCHOS GPCR-plant-like transporter interplay senses cholesterol levels to modulate cell growth, newly druggable
Beyond GPCR… Expanding the GPCR Frontier
It was also found that GSEC advances the consumption of GCPRs (which are a type of receptor involved in many important biological processes). GPCRs are commonly believed to function independently, but the researchers realized that with LYCHOS, GPCRs were paired with a different membrane protein—a transporter—to form a hybrid of GPCR.
“GPCRs are now known to cross-talk with many other membrane proteins including transporters, and this finding further expands the repertoire of potential GPCR hybrids,” added fellow co-lead author Associate Professor Michelle Halls. Overall, this discovery paves the way for new insights into how GPCRs form across human cells.
Opening Up New Avenues in Drug Discovery
To a deeper level, the resolution of LYLYCHOS structures through cryo-EM technology has important repercussions on drug development. Through this cutting-edge technique, the researchers and drug discoverers all over the world have gained a detailed insight into LYCHOS and how it functions as a cholesterol- sensor and modifier.
“Gathering any new structural information on LYCHOS is very exciting as it now potentially enables the design of therapeutic drugs that are able to block things like unrecognized cell proliferation and tumor growth and spread, or disrupted cholesterol metabolism (e.g., observed in some neurological states), ultimately targeting a variety of diseases,” Associate Professor Halls noted. The team now is working on creating a novel class of cell growth inhibitors designed to inhibit LYCHOS and treat myriad diseases caused by runaway cell proliferation.
