Biochemical controls: intrinsically disordered proteins (Introduction)

by David Turell , Wednesday, November 06, 2024, 16:49 (15 days ago) @ David Turell

Form membraneless organelles:

https://www.sciencealert.com/tiny-organs-hiding-in-our-cells-could-challenge-the-origin...

"I was introduced to membraneless organelles, formally called biomolecular condensates, a couple years ago when students in my lab observed some unusual blobs in a cell nucleus.

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"To get a sense of what a biomolecular condensate looks like, imagine a lava lamp as the blobs of wax inside fuse together, break apart and fuse again. Condensates form in much the same way, though they are not made of wax. Instead, a cluster of proteins and genetic material, specifically RNA molecules, in a cell condenses into gel-like droplets.

"Some proteins and RNAs do this because they preferentially interact with each other instead of their surrounding environment, very much like how wax blobs in a lava lamp mix with each other but not the surrounding liquid. These condensates create a new microenvironment that attracts additional proteins and RNA molecules, thus forming a unique biochemical compartment within cells.

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"As of 2022, researchers have found about 30 kinds of these membraneless biomolecular condensates. In comparison, there are around a dozen known traditional membrane-bound organelles.

"Although easy to identify once you know what you are looking for, it's difficult to figure out what biomolecular condensates exactly do. Some have well-defined roles, such as forming reproductive cells, stress granules and protein-making ribosomes. However, many others don't have clear functions.

"Nonmembrane-bound organelles could have more numerous and diverse functions than their membrane-bound counterparts. Learning about these unknown functions is affecting scientists' fundamental understanding of how cells work.

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"the mantra for biochemists has been that protein structure equals protein function. Basically, proteins have certain shapes that allow them to perform their jobs.

"The proteins that form biomolecular condensates at least partially break this rule since they contain regions that are disordered, meaning they do not have defined shapes. When researchers discovered these so-called intrinsically disordered proteins, or IDPs, in the early 1980s, they were initially confounded by how these proteins could lack a strong structure but still perform specific functions.

"Later, they found that IDPs tend to form condensates. As is so often the case in science, this finding solved one mystery about the roles these unstructured rogue proteins play in the cell only to open another deeper question about what biomolecular condensates really are.

"Researchers have also detected biomolecular condensates in prokaryotic, or bacterial, cells, which traditionally were defined as not containing organelles. This finding could have profound effects on how scientists understand the biology of prokaryotic cells.

"Only about 6 percent of bacterial proteins have disordered regions lacking structure, compared with 30 percent to 40 percent of eukaryotic, or nonbacterial, proteins. But scientists have found several biomolecular condensates in prokaryotic cells that are involved a variety of cellular functions, including making and breaking down RNAs.

"The presence of biomolecular condensates in bacterial cells means that these microbes aren't simple bags of proteins and nucleic acids but are actually more complex than previously recognized."

Comment: the inner workings of a living cell are becoming overwhelmingly complex as we unravel them. The rule of protein shape making the function is stretched but not broken.

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Origin of life author's aside:

"Biomolecular condensates are also changing how scientists think about the origins of life on Earth.

"There is ample evidence that nucleotides, the building blocks of RNA and DNA, can very plausibly be made from common chemicals, like hydrogen cyanide and water, in the presence of common energy sources, like ultraviolet light or high temperatures, on universally common minerals, like silica and iron clay.

"There is also evidence that individual nucleotides can spontaneously assemble into chains to make RNA. This is a crucial step in the RNA world hypothesis, which postulates that the first 'lifeforms' on Earth were strands of RNAs.

"A major question is how these RNA molecules might have evolved mechanisms to replicate themselves and organize into a protocell. Because all known life is enclosed in membranes, researchers studying the origin of life have mostly assumed that membranes would also need to encapsulate these RNAs.

"This would require synthesizing the lipids, or fats, that make up membranes. However, the materials needed to make lipids likely weren't present on early Earth.

"With the discovery that RNAs can spontaneously form biomolecular condensates, lipids wouldn't be needed to form protocells. If RNAs were able to aggregate into biomolecular condensates on their own, it becomes even more plausible that living molecules arose from nonliving chemicals on Earth."

Comment: ool folks are always so hopeful of a solution.