Biological complexity: protein folding creates life (Introduction)

by David Turell , Wednesday, February 03, 2021, 17:55 (1389 days ago) @ David Turell

Some proteins have more than one shape to perform different functions:

https://www.quantamagazine.org/metamorphic-proteins-change-their-folds-for-different-jo...

"Proteins are molecular origami at its finest. Classically, a protein is imagined as a chain of amino acids that folds into a single stable configuration, one that evolution has selected over the ages for a particular function. But in the last few years, biophysicists have learned how numerous and extraordinary the exceptions to that rule are — including some two-faced proteins that can refold as needed in an instant.

"First came the discovery of a special class of fold-switching proteins that have more than one stable conformation and can perform two different functions. Such proteins might seem unlikely to evolve because natural selection for the first shape and function could easily be detrimental to the second, and vice versa. Yet fold-switching proteins, of which about 100 are currently known, have evolved in all kingdoms of life and perform more than 30 types of biological functions. (my bold)

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"Researchers at the Medical College of Wisconsin have now reconstructed the evolutionary history of a metamorphic human protein called XCL1. In one shape, it acts as a signaling molecule called a chemokine, binding to receptors on white blood cells and recruiting them to fight infections. But it can easily switch to a second shape that kills bacterial invaders as an antibiotic.

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"The fact that the ancestors exhibited the two folds unevenly while the modern XCL1 exhibits both in equal proportion strongly suggests that the switching property “is not an accident or an artifact. It’s something that must have been beneficial and improved the fitness of the organism, because it appeared to be selected for,” said Brian Volkman, a biophysicist and senior author of the study, which appeared in Science on January 1. (Comment here: pure Darwin. Design fits also)

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"But why would metamorphosis be better than having two specialized proteins? The scientists theorize in their paper about a couple of linked possibilities. If a single protein can do double duty, it spares the cell from transcribing, translating and maintaining more than one gene. But the more compelling advantage may be that the protein’s ability to transform may give the body a more dynamic way to control its defenses against bacteria.

"Because XCL1 can adopt its two folded forms with equal probability, it can switch between them faster than once per second. But changes in the temperature or salt concentration or the introduction of binding partners can change that equilibrium. For example, around microbial pathogens, more of the XCL1 proteins get stuck in the conformation that interacts with the microbial membranes, shifting the balance toward that fold. Elsewhere in the body, the protein can adopt the other fold more often and bind to the receptors on white blood cells to mobilize them. (my bold)

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"Metamorphic fold-switching also enables the body to eliminate an unwanted function simply by flipping the protein’s structure to the other conformation, rather than having to wait for the protein to be degraded. “This has the elegance of simplicity,” Volkman said.

"The arguments for these apparent advantages can seem so convincing that they raise the question of why XCL1 is the only chemokine that evolved metamorphic folding. The researchers acknowledge that this is still a mystery."

Comment: Once again note high speed requirements, while the free floating molecules can make mistakes..