A groundbreaking study conducted by researchers at the University of Utah Health and Brigham Young University utilized cryo-electron microscopy (cryo-EM) to investigate the folding of a protein called Gβ5. This protein is involved in G protein signaling, a ubiquitous process underlying numerous essential cell functions. Notably, approximately one-third of all known pharmaceuticals target this system. Like many proteins, Gβ5 requires a chaperone to fold correctly, and observing the interaction between the two molecules over time proved challenging.
By employing cryo-EM, the researchers were able to capture snapshots of Gβ5 and its chaperone, CCT, during the folding process. After isolating samples and flash-freezing the proteins, they used an electron microscope to obtain images at near-atomic resolution. Each protein molecule was frozen at a distinct stage along the folding process, allowing the researchers to piece together a “movie” of the folding process by ordering individual snapshots into their respective places along a continuum.
The study’s findings challenged the prevailing theory that chaperones act as protective cages for new proteins, providing a safe environment for self-folding and preventing interactions with other molecules that could disrupt the process. Instead, the researchers found that CCT played a much more active role in guiding the folding process, interacting with specific parts of Gβ5 to initiate folding. This revelation suggests that such specific interactions may be common among chaperone molecules and the proteins they assist.