Biological complexity: shape shifting proteins (Introduction)

by David Turell , Friday, May 12, 2017, 20:31 (2531 days ago) @ David Turell

Not all proteins are fixed in shape. Those that don't have a fixed form are vital to the functions of life:

https://www.quantamagazine.org/20170118-disordered-proteins/?utm_source=Quanta+Magazine...

"...recently, however, biologists have begun paying attention to these shapeshifters. Their findings are tearing down the structure-function dogma.

"Proteins are chains of strung-together amino acids, and recent studies estimate that up to half of the total amino acid sequence that makes up proteins in humans doesn’t fold into a distinct shape.

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"This fluidity — dubbed “intrinsic disorder” — endows proteins with a set of superpowers that structured proteins don’t have. Folded proteins tend to bind to their targets firmly, like a key in a lock, at just one or two spots, but their more stretched-out wiggly cousins are like molecular Velcro, attaching lightly at multiple locations and releasing with ease. This quick-on-quick-off binding’s effect in the cell is huge: It allows intrinsically disordered proteins — or IDPs, for short — to receive and respond to a slew of molecular messages simultaneously or in rapid succession, essentially positioning them to serve as cellular messaging hubs, integrating these multiple signals and switching them on and off in response to changes in the cell’s environment and to keep cellular processes ticking along as they should.

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" IDPs help regulate the gas and brake pedals for producing proteins from the DNA code, according to evidence that has accumulated over the past decade, as well as the process by which cells divide. IDPs may also provide cues that allow cells to take on traits specific to different tissues or parts of the body. In other words, they may somehow help make a blood cell a blood cell and a muscle cell a muscle cell.

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"Dunker’s analysis revealed that disordered proteins had very different sequences of amino acids than structured ones. When he looked for these differences in databases of sequenced proteins, a surprisingly high number of disordered suspects popped out. Even more interesting, a higher percentage of the protein sequence is disordered in more complex organisms — for example, about 20 percent of the amino acids in the bacterium Escherichia coli are disordered, but the percentage is at least twice as high in humans.

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"Protein disorder occurs along a continuum. At one end of the spectrum lie proteins like p21, which fold on contact with other proteins. At the other end are ones that remain limp and floppy, like wet noodle strands, never taking on a shape. Researchers still don’t know how this range corresponds to their versatile functions, but being more like a string than like a lump with keyholes means that a protein can make many contacts with other molecules to regulate the network of signals that drives the cell. “You have all these on-off switches for all kinds of functions,” said Dunker.

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"When they examined a database of around 5,000 human proteins, they found that most unstructured proteins were expressed in small quantities and quickly destroyed after they had done their job.

"The reason cells regulate their production so tightly and make sure they turn over so quickly is that IDPs pack a huge punch, Babu said. Having too many would be like having a glut of upper management  — with too many people shouting commands, productivity grinds to a halt. Extend that logic to a cell, though, and things can get ugly: Because IDPs regulate how different components of the cell communicate with one another, having extra copies floating around could leave them sending signals that shouldn’t get sent. “These proteins are so dangerous that you can’t afford not to regulate them,” Babu said.

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"When a cell produces too many of these proteins, they found, it dies.

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"For him the turning point came five years ago, when a colleague showed him data suggesting that some disordered proteins can form liquid droplets that briefly exist suspended in the fluid of the cell. Researchers still don’t know exactly how or why this process occurs, but some speculate that it brings molecules together for signaling.

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"Hurley speculates that these disordered regions act like a weak glue, creating just the right level of cohesion — not too rigid and not too loose — to bring together the molecular components needed for autophagy" [cell death].

Comment: So living cells have both fixed and disordered proteins to run the processes of life. Too complex for chance development. This is different than the Kinesin transport proteins.