Biological complexity: an enzyme controls cellular stress (Introduction)

by David Turell , Saturday, March 11, 2023, 20:33 (413 days ago) @ David Turell

Latest research:

https://phys.org/news/2023-03-enzyme-ate1-plays-role-cellular.html

"...Aaron T. Smith and colleagues discovered that this enzyme plays an important role in the cellular stress response.

"The enzyme is named ATE1, and it belongs to a family of enzymes called arginyl-tRNA transferases. These enzymes add arginine (an amino acid) to proteins, which often flags the proteins for destruction in the cell. Destroying proteins that are misfolded, often as a result of cellular stress, is important to prevent those proteins from wreaking havoc with cellular function. An accumulation of malfunctioning proteins can cause serious problems in the body, leading to diseases like Alzheimer's or cancer, so being able to get rid of these proteins efficiently is key to long-term health.

"The new paper demonstrates that ATE1 binds to clusters of iron and sulfur ions, and that the enzyme's activity increases two- to three-fold when it is bound to one of these iron-sulfur clusters. What's more, when the researchers blocked cells' ability to produce the clusters, ATE1 activity decreased dramatically. They also found that ATE1 is highly sensitive to oxygen, which they believe relates to its role in moderating the cell's stress response through a process known as oxidative stress.

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"Around the same time, another group also published a slightly different ATE1 structure. The other group's structure had a zinc ion (another metal) bound in place of the iron-sulfur cluster. With the zinc in place, one key amino acid is rotated about 60 degrees. It might seem inconsequential, but Smith believes that rotation, which he presumes is similar with the cluster, is the key to the cluster's role in ATE1's function.

"The rotated amino acid is directly adjacent to where a protein would interact with ATE1 to be modified, ultimately flagging it for degradation. Changing the angle of that amino acid changes the shape of the location the protein would bind "very subtly," but changes its activity "more than subtly," Smith says."

Comment: another example of a complex enzyme doing its job. At issue is the usual question. How did this happen? Enzymes like this are giant molecules with very specific structure made from many thousands of amino acids. Not by chance. Must be designed for its job.