Biochemical controls: strange strings on proteins function (Introduction)

by David Turell , Monday, October 02, 2023, 23:08 (416 days ago) @ David Turell

They are called intrinsically disordered regions (IDRs):

https://phys.org/news/2023-10-reveals-overlooked-proteins-critical-fundamental.html

"Around half of all proteins have stringy, unstructured bits hanging off them, dubbed intrinsically disordered regions, or IDRs. Because IDRs have more dynamic, "shape-shifting" geometries, biologists have generally thought that they cannot have as precise of a fit with other biomolecules as their folded counterparts, and as such, assumed these thread-like entities may contribute less significantly to overall protein function.

"Now, a multi-institutional collaboration has uncovered how a key aspect of cell biology is controlled by IDRs. Their study, published in the journal Cell, reveals that IDRs have specific and important interactions that play a central role in chromatin regulation and gene expression, essential processes across every living cell.

"The researchers focused on disordered regions of the human cBAF complex, a multi-component group of proteins in the nucleus that works to open up the densely coiled-up DNA inside cells called chromatin, enabling genes along DNA to be expressed and turned into proteins. Mutations in the IDRs of one family of cBAF subunits, ARID1A and ARID1B, which are highly frequent in cancer and neurodevelopmental disorders, throw chromatin remodeling and gene expression out of whack, suggesting IDRs are anything but trivial extras. (my bold)

"In particular, the study revealed that the IDRs form little droplets called condensates that separate out from surrounding cellular fluid, just like drops of oil in water. The specific interactions that happen in these condensates allow proteins and other biomolecules to congregate in particular locations to carry out cellular activities. While scientists have shown that condensates perform a myriad of tasks, it was not known if these special liquid droplets had any role in chromatin remodeling, nor whether their specific amino acid sequences served specific functions.

"Researchers from Princeton, the Dana-Farber Cancer Institute and Washington University in St. Louis teamed up to study the effects of different mutations in the ARID1A/B IDRs on the ability of the cBAF protein complex to form condensates and recruit partner proteins needed for gene expression.

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"'For the first time, we've shown that intrinsically disordered regions are fundamentally important for operation of a key chromatin remodeling complex, the cBAF complex" said Amy Strom, co-lead author of the study. "Our findings should be applicable to IDRs in general and could have significant implications for how cells do everything they do."

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"Brangwynne, whose lab has studied disordered sequences and their role in forming condensates for years, said "Intrinsically disordered regions are everywhere in the vast catalog of human and other organisms' proteins, and they're playing central roles in physiology and disease in ways we're just starting to understand.'"

Comment: an important new finding telling us that all proteins, like all DNA are there for a purpose. Human invented 'junk DNA' and now it is gone. Ignoring IDR's (note my bold) is simply humans thinking they are smarter than the designer.