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Study: Knowing how cells dispose of unwanted material is key to potential new treatments.

Graphical summary. Credit: The molecular cell (2024). DOI: 10.1016/j.molcel.2024.01.022

Are you sick and tired of being sick? A UNLV-led research team is exploring whether the reason we sometimes feel sick in the first place is because our body’s cells are affected by the junk that accumulates inside them.

Gary Kliger, professor and chair of UNLV’s Department of Chemistry and Biochemistry, along with Brenda Schulman, director of the Munich-based Max Planck Institute of Biochemistry, and their teams are working on ways to help our bodies fight disease. Help hunt and destroy. causes protein.

He is the author of a new study, “Colin-Ring Ligases Target Substrates with Geographically Optimized Catalytic Partners”. published In the journal The molecular cell, which furthers our understanding of how enzymes called cullin-RING ligases (or CRLs) help cells get rid of proteins that are no longer needed. The findings also point to a potential Achilles heel for proteins that make us sick.

“Clin-ring-ligases (CRLs) are complex nanomachines that are critical to the cell’s complex disposal and recycling system,” Shulman said. “CRLs tag defective, toxic, or excessive proteins with a small protein called ubiquitin, and mutations or defects that disrupt CRLs are often associated with diseases, such as developmental disorders or cancer.”

The research team argues that because CRLs have key functions in maintaining the well-being of our cells, defining and understanding them is of fundamental importance. .

“This is very important work. For example, during the COVID-19 lockdown, some people will remember that at least some cities have piles of garbage on the sidewalks, creating a health crisis. ” says Kliger. “The same is true for our cells, and At least in part this may be due to our disposal system not working properly.”

Learning more about how cells are using these processes to shed unnecessary or unwanted materials could potentially accelerate drug discovery studies.

“Researchers have already made amazing progress toward ‘hijacking’ CRL to find disease-causing proteins. Many believe this is the next big innovation in drug discovery.” . “And by further revealing how CRLs function in our cells, scientists can use this knowledge to better understand human disease and support this new platform for drug discovery.”

CRLs work by labeling proteins targeted for destruction with small proteins called ubiquitin, and Kliger’s lab was the first to show that ubiquitin transfer rates approach speeds that are some of the fastest in organisms. Counteracts known reactions. The results of the current work tell us more about how cells are able to be selective about what they get rid of, and that proteins don’t accidentally end up in the trash.

Over the past 20 years, thousands of scientists have spent billions of dollars researching the concept of treating human disease by marrying enzymes that The destruction of proteins that lead to disease.

There is a great selection of CRLs. Specialist, CRL-dependent drugs to promote the destruction of disease-causing proteins are already in the clinic and could receive FDA approval within one to two years. The work of Kleiger, Schulman and their colleagues moves the needle toward concrete solutions.

The new research is just the latest from the Kliger and Shulman labs to show snapshots of CRLs during the process of labeling proteins for destruction. Earlier this month, Kleiger, Schulman and colleagues published a paper. In the journal Structural and molecular biology of nature That allowed scientists to imagine Precise labeling mechanism, catalyzed by CRLs for the first time.

More information:
Jerry Li et al., Cullin-RING ligases employ geometrically optimized catalytic partners for substrate targeting, The molecular cell (2024). DOI: 10.1016/j.molcel.2024.01.022

Reference: Learning how cells dispose of unwanted materials is key to potential new treatments, scientists say (2024, Feb. 21) February 21, 2024 https://phys.org/news/2024-02-cells Retrieved from -dispose-unwanted-materials- key.html

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