Biological complexity: actin fibers discovery and unknowns (Introduction)

by David Turell , Saturday, June 10, 2023, 17:22 (322 days ago) @ David Turell

New discoveries of design for specific functions:

https://www.sciencedaily.com/releases/2023/06/230608120933.htm

"Now, researchers from the Perelman School of Medicine at the University of Pennsylvania have revealed key atomic structures of the ends of the actin filament through the use of a technique called cryo-electron microscopy (cryo-EM).

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"Actin is the most abundant protein inside the cells of higher organisms, such as animals. It serves as the building-block for long, thin structures called filaments, which provide key structural support as part of the cell "cytoskeleton," the system that gives cells their shape and polarity. Rapid changes in actin filaments underlie key cellular events such as movement along surfaces, cell-to-cell contact, and cell division. Actin filaments also are major elements in muscle fibers.

"'The results of our study provide a mechanistic understanding of a process we have known about for more than 40 years, referred to as filament treadmilling, and impacts how we view the cellular roles of actin in health and disease," said the study senior author Roberto Dominguez, PhD, the William Maul Measey Presidential Professor of Physiology at Penn.

"The dynamics of actin filaments are governed largely by the "treadmilling" process, through which individual actin proteins are shed from one filament end, known as the pointed end, and added at the other, barbed end. Actin filaments can be stabilized by distinct so-called "capping" proteins that bind to the filament ends to stop further addition or loss of individual actin proteins. Many other proteins also bind to the barbed and pointed ends of the actin filament. But the structural details determining the specificity of these interactions -- the details that explain why these two ends function so differently -- have been murky.

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"With artificial intelligence (AI) assistance, the researchers were able to focus on the ends of the filaments instead of their middle, as had previously been the norm in similar research. By doing so, they identified hundreds of thousands of filament end views, allowing them to obtain near-atomic scale reconstructions. These revealed a "flat" actin shape, or conformation, at the uncapped barbed end, versus a "twisted" conformation at the uncapped pointed end.

"The data also detailed the structural changes induced by two actin filament-capping proteins, CapZ at the barbed end and tropomodulin at the pointed end. These are the two proteins found at the ends of the filament in skeletal and cardiac muscles, playing an essential role in the stabilization of actin filaments in muscle fibers, and, without these proteins, our muscles would fall apart."

Comment: more irreducible complexity requiring design.