RESEARCH: CANCER
FOLDING PROJECT #16450 PROFILE

This project studies how G proteins work, especially when they're active and causing problems like uveal melanoma (eye cancer). By simulating an active form of a G protein called Gq, scientists hope to learn why some treatments don't work against the active form and find new ways to stop these diseases.

This project seeks to understand G protein inhibition in the treatment of uveal melanoma and other G protein related diseases.

G proteins are molecular switches regulate biological functions like sight, smell, and memory.

This pivotal role makes G proteins essential players in physiology and pathophysiology.

However, when G proteins mutate, they result in a variety of diseases from cancer to heart disease.

For example, a single mutation in the Gq protein is known to cause uveal melanoma, a cancer in the iris of our eyes that remains largely untreatable short of removing the eye. This project is simulating one of the G protein family isoforms, Gq, but in the ACTIVE form, bound to GTP.

Other projects are simulating Gq, and other G proteins, in their "inactive" form, bound to GDP.

The presence of the third phosphate in GTP is sufficient to convert G proteins into their active form.

However, the ensemble of structures they adopt are not completely parsed out.

By simulating the active form of Gq and comparing to other structures, we hope to provide a better understanding of G protein function.

Furthermore, existing inhibitors of G proteins do not inhibit the GTP bound form, only the GDP-version, and understanding the "active ensemble" might provide a clearer picture as to why.

G protein

A family of proteins that act as molecular switches in cellular signaling.

G proteins are essential for many biological processes, such as vision, smell, and memory. They work by binding to guanine nucleotides (GTP or GDP). When bound to GTP, they are active and transmit signals within the cell. When bound to GDP, they are inactive. Mutations in G proteins can lead to various diseases, including cancer.

uveal melanoma

A type of eye cancer that affects the uvea, the middle layer of the eye.

Uveal melanoma is a rare but serious form of eye cancer. It typically develops in the iris, ciliary body, or choroid. Symptoms may include changes in vision, floaters, or pain. Treatment options depend on the stage and location of the tumor and may include surgery, radiation therapy, or chemotherapy.

GTP

Guanosine triphosphate

GTP is a molecule that provides energy for cellular processes. It's a key player in signaling pathways, where it binds to proteins like G proteins, activating them.

GDP

Guanosine diphosphate

GDP is a molecule related to GTP. When G proteins are bound to GDP, they are inactive.

inhibitor

A substance that reduces the activity of an enzyme or other biological molecule.

Inhibitors are used in medicine and research to block specific processes within cells. They can target enzymes involved in disease pathways or regulate cellular signaling.