Biochemical controls: chaperones control proteins (Introduction)

by David Turell , Tuesday, October 08, 2024, 20:00 (9 days ago) @ David Turell

In helping with foldings:

https://phys.org/news/2024-10-nanopore-technique-mechanism-chaperone-proteins.html

"Proteins control most of the body's functions, and their malfunction can have severe consequences, such as neurodegenerative diseases or cancer. Therefore, cells have mechanisms in place to control protein quality.

"In animal and human cells, chaperones of the Hsp70 class are at the heart of this control system, overseeing a wide array of biological processes. Yet, despite their crucial role, the precise molecular mechanism of Hsp70 chaperones has remained elusive for decades.

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"Proteins need to fold into specific three-dimensional shapes to function correctly. Among their several roles, chaperone proteins like Hsp70s typically assist the correct folding of proteins. To successfully perform these tasks, Hsp70s need to forcefully manipulate the structure of the proteins, extracting them from aggregates that had formed spontaneously or by facilitating protein translocation into key cell compartments, such as mitochondria.

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"In the Entropic Pulling mechanism, the chaperone, by pulling on the target protein, increases its range of movement, generating what is known as an entropic force. Verena Rukes, Ph.D. student and the leading author of the study, explains, "Our analysis estimated the strength of Entropic Pulling to be approximately 46 pN over distances of 1 nm, indicating a remarkably strong force at the molecular level."

"Prof. Paolo De Los Rios from the Institute of Physics and Institute of Bioengineering at EPFL states, "Our theory proposed in 2006 was accounting for most of the physics of the system comprising Hsp70, the translocating protein and the translocation pore, but in the end, it remained a theory, even if in indirect agreement with most observations.

"'Thanks to the beautiful work of Prof. Chan Cao and her team, we now have direct proof of it and, which is most important, a quantitative estimate of its strength, which turns out to be remarkably high, further explaining why Hsp70s are so effective at changing the structure of their target proteins.'"

Comment: at the nano-gram level this is an amazing amount of force. With one protein as primary and another as secondary there is much room for mistakes from freely acting proteins. These are mistakes by proteins, not their designer.