Biochemical controls: cells on the edge of chaos (Introduction)

by David Turell , Wednesday, September 18, 2024, 18:42 (64 days ago) @ David Turell

The role of intrinsically disordered proteins:

https://evolutionnews.org/2024/09/embrace-the-chaos-cells-harness-disorder-for-function/

"There’s news on the weird proteins that refuse to fold — the “intrinsically disordered proteins” (IDPs) that flop and flail around like unsophisticated dancers in the cellular ballet.

"These dynamic, ever-changing proteins have long fallen through the cracks of conventional structural biology methods and have been excluded or ignored for their staunch defiance of a central tenet in protein science: structure defines function. However, a growing body of evidence found that these are not rare proteins performing odd jobs in the underbelly of our cells nor are they evolutionary junk hoarded in the proteome.They are well-known entities that are deeply entrenched in regulatory biology.

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"By remaining loose instead of compact, IDPs can “take on many different conformations.” That confers multifunctionality on these proteins, giving the cell flexibility over static proteins.

"It’s been difficult to study IDPs through traditional methods, but new techniques are gradually bringing them into focus. Scientists are finding many more IDPs than thought. Proteins can now be classified on a spectrum from ordered to disordered, some fully compacted, some fully “disordered,” and some with folded parts and disordered parts.

"Proteins with disorder aren’t relegated to the sidelines of cellular activity. On the contrary, disordered proteins are stalwarts of cellular communication. “They have so many different functions. It’s incredible,” said Heller. Their conformational freedom facilitates a kind of functional promiscuity that provides cells with multiplexed and flexible recognition and response systems. In line with this, these malleable machines are often hubs for essential cellular processes, including gene regulation, cell division, molecular recognition, and cell signaling. “In all of those cases, you need something sensitive to its environment [that] needs to know when to switch on [and] when to switch off,” said Heller.

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"The discovery of membraneless organelles is changing all that. Given names like speckles, droplets, and condensates, these are ad hoc, rapidly forming and disbanding groupings of molecules that I likened to temporary work groups gathering within the floor space of a large office.

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"The condensates appear to form and disperse due to phase changes in the medium, like oil droplets forming in water. And as Caltech found, getting the right phase at the right time and place, and recruiting the right “employees” for the meetings, appears to be a job for noncoding RNAs — previously dismissed as junk.

"Duke University is now finding evidence that these “understudied protein blobs” create their own electrochemical environment. And this, in turn, affects the charge distribution of the entire cell.

"Now, in a new study published September 10 in the journal Cell, researchers from Duke University and Washington University in St. Louis have shown that the formation of biological condensates affects cellular activity far beyond their immediate vicinity. The results show that they may be a previously missing mechanism by which cells modulate their internal electrochemistry. And those internal controls, in turn, affect the cellular membrane, which allows these unassuming blobs to affect global traits and outcomes such as resistance to antibiotics.

"In other words, condensates can harness the phase changes to control their internal electrostatic environment. This, in turn, affects electrostatic conditions of the entire cell. In effect, it provides another layer of intercellular communication.

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“Even a tiny number of these condensates centrally distributed well away from the cell membrane can create a chain reaction that can change this global property,” explained Yifan Dai, an assistant professor of biomedical engineering and a member of the Center for Biomolecular Condensates at Washington University in St. Louis, who conducted the research as a postdoctoral researcher at Duke. “This paper shows there is no escape from these effects. As long as these tiny blobs form, many things are influenced, even gene regulation in a global scale."

Comment: cells are under electrostatic controls while everything is actually loose actively following directive forces. Rigid compartmentalization does not allow life to form. This key point is why I always say mistakes will happen and dhw pounces on them to disparage God. God gave us life in this form because it is the only way life works. There is no take it or leave it here. It is an answer to theodicy in which perfection is demanded. It doesn't exist on the edge of chaos.