Biological complexity: unfolding used proteins (Introduction)

by David Turell , Thursday, June 27, 2019, 20:24 (1976 days ago) @ David Turell

Cells must unfold proteins to remove them:

https://phys.org/news/2019-06-cells-unfold-proteins.html

"A happy cell is a balanced cell, but for every stupendously twisted protein it creates, it must tear the old ones asunder. That means untangling a convoluted pretzel-like mass for recycling. Cdc48 plays a critical role in unraveling the spent proteins.

"'Cdc48 is the swiss army knife of the cell and can interact with so many different substrates," said Peter Shen, Ph.D.,

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"In the study, the research team purified Cdc48 directly from yeast cells (Saccharomyces cerevisiae) and took snapshots of the purified particles in different configurations after it was flash frozen using cryogenic electron microscopy (cryo-EM).

"'The cells are already doing the hard work for us by making these complexes," Shen said.
"Because this method is so fast, we have captured Cdc48 in the act of unfolding a protein substrate."

"Using this approach, the research team demonstrated how Cdc48 unfolds the protein by threading it through a central pore of the complex, using a hand-over-hand conveyor-like movement. The recycled tangle they were imaging was a mystery until collaborators at Brigham Young University applied mass spectrometry proteomics to the same harvested complex to unmask the anonymous proteinan inactive protein phosphatase 1 complex.

"Shen believes these results are applicable to human cells, because Cdc48 is highly conserved.

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"The research team was unable to visualize the entire complex because Cdc48 interacts with multiple binding partners almost simultaneously. This efficient multitasking blurs the reconstruction; however, Shen wants to continue to explore how Cdc48 manages to bind with so many partners at roughly the same time."

Comment: I process of this complexity can not have arrived by chance.