Biological complexity: ATP rotor design shown (Introduction)

by David Turell , Wednesday, September 16, 2020, 19:40 (1529 days ago) @ David Turell

ATP is used all through life to provide an energy supply. Its complex structure is now known:

https://www.sciencedaily.com/releases/2020/09/200914114134.htm

"ATP synthase is also referred to as complex V of the respiratory chain, a series of protein complexes in the membrane of mitochondria. This respiratory chain creates a proton gradient, which the ATP synthase uses to make ATP. Previously, Sazanov was the first to solve the protein structure of bacterial complex I, and the first to solve the structure of a mammalian complex I. In the new study, Sazanov and lab members Gergely Pinke and Long Zhou turned to mammalian complex V, the final unsolved structure in the mammalian respiratory chain. "F1Fo-ATP synthase is one of the most important enzymes on Earth. It provides energy for most life forms, including us humans, but until now, we didn't know fully how it works," explains Sazanov.

***

"In their high-resolution structure of Fo, the researchers found that the c-ring is plugged by two lipids, one from each side of the membrane. While the top (facing F1) lipid rotates along with the shaft, the bottom lipid does not rotate, as it is likely connected to the Fo domain via a "hook apparatus."

"This newly uncovered structure sheds light on a controversy in biology: how and where the so-called permeability transition pore opens. This pore is linked with cell death, and opens for example during strokes and heart attacks. So far, it was known that the pore forms in mitochondria in response to high levels of Calcium, but the pore's exact location remained unknown. Now, using the fully solved structure of F1Fo, Sazanov and his group can describe how the pore forms in F1Fo-ATP synthase: When Calcium binds in the F1 subunit, a large conformational change is induced. The complex has to accommodate this change, and in doing so, pulls on the hook apparatus. The apparatus in turn pulls out the lipid plug on the bottom side of the Fo, initiating pore opening. "When the pore is open for a longer period of time, the c-ring is destabilized and pore formation becomes irreversible," explains Sazanov. "This model is consistent with all available data from mutants. To be fully sure that this is how the permeability transition pore forms, one would need to solve the structure of ATP synthase during Calcium-induced transitions, which we are doing now.'"

Comment: Highly complex. Obviously designed.