Biochemical controls: garbage disposal (Introduction)

by David Turell , Saturday, August 26, 2023, 20:33 (245 days ago) @ David Turell

Getting rid of old proteins:

https://www.sciencedaily.com/releases/2023/08/230824150719.htm

"Short-lived proteins control gene expression in cells to carry out a number of vital tasks, from helping the brain form connections to helping the body mount an immune defense. These proteins are made in the nucleus and are quickly destroyed once they've done their job.

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"...the researchers homed in on midnolin as a protein that helps break down both transcription factors. Follow-up experiments revealed that in addition to Fos and EGR1, midnolin may also be involved in breaking down hundreds of other transcription factors in the nucleus.

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"They established that midnolin has a "Catch domain" -- a region of the protein that grabs other proteins and feeds them directly into the proteasome, where they are broken down. This Catch domain is composed of two separate regions linked by amino acids (think mittens on a string) that grab a relatively unstructured region of a protein, thus allowing midnolin to capture many different types of proteins. (my bold)

"Of note are proteins like Fos that are responsible for turning on genes that prompt neurons in the brain to wire and rewire themselves in response to stimuli. Other proteins like IRF4 activate genes that support the immune system by ensuring that cells can make functional B and T cells.

"'The most exciting aspect of this study is that we now understand a new general, ubiquitination-independent mechanism that degrades proteins," Elledge said.

"In the short term, the researchers want to delve deeper into the mechanism they discovered. They are planning structural studies to better understand the fine-scale details of how midnolin captures and degrades proteins. They are also making mice that lack midnolin to understand the protein's role in different cells and stages of development.

"The scientists say their finding has tantalizing translational potential. It may offer a pathway that researchers can harness to control levels of transcription factors, thus modulating gene expression, and in turn, associated processes in the body.

"'Protein degradation is a critical process and its deregulation underlies many disorders and diseases," including certain neurological and psychiatric conditions, as well as some cancers, Greenberg said."

Comment: These short-lived proteins know what to grab. We do not know how they know what to do. Designed automatic ionic attraction is one way, but another is the 'Catch domain' which acts as a lock and key connection. All automatic.