Biological complexity: architecture of human membrane pore (Introduction)

by David Turell , Friday, June 10, 2022, 20:37 (897 days ago) @ David Turell
edited by David Turell, Friday, June 10, 2022, 20:47

Took over two years to piece it out:

https://phys.org/news/2022-06-decoding-key-cell-atom.html

"Among those pieces of machinery, and one of the most complex, is something known as the nuclear pore complex (NPC). The NPC, which is made of more than 1,000 individual proteins, is an incredibly discriminating gatekeeper for the cell's nucleus, the membrane-bound region inside a cell that holds that cell's genetic material. Anything going in or out of the nucleus has to pass through the NPC on its way.

"The NPC's role as a gatekeeper of the nucleus means it is vital for the operations of the cell. Within the nucleus, DNA, the cell's permanent genetic code, is copied into RNA. That RNA is then carried out of the nucleus so it can be used to manufacture the proteins the cell needs. The NPC ensures the nucleus gets the materials it needs for synthesizing RNA, while also protecting the DNA from the harsh environment outside the nucleus and enabling the RNA to leave the nucleus after it has been made.

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"Working their way through the proteins in this way eventually produced the final result of their paper: a 16-protein wedge that is repeated eight times, like slices of a pizza, to form the face of the NPC.

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"In the other paper, titled "Architecture of the linker-scaffold in the nuclear pore," the research team describes how it determined the entire structure of what is known as the NPC's linker-scaffold—the collection of proteins that help hold the NPC together while also providing it with the flexibility it needs to open and close and to adjust itself to fit the molecules that pass through.

"Hoelz likens the NPC to something built out of Lego bricks that fit together without locking together and are instead lashed together by rubber bands that keep them mostly in place while still allowing them to move around a bit.

"I call these unstructured glue pieces the 'dark matter of the pore,'" Hoelz says. "This elegant arrangement of spaghetti noodles holds everything together."

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"The assembly of the NPC's outer face also helped solve a longtime mystery about the nuclear envelope, the double membrane system that surrounds the nucleus. Like the membrane of the cell within which the nucleus resides, the nuclear membrane is not perfectly smooth. Rather, it is studded with molecules called integral membrane proteins (IMPs) that serve in a variety of roles, including acting as receptors and helping to catalyze biochemical reactions.

"Although IMPs can be found on both the inner and outer sides of the nuclear envelope, it had been unclear how they actually traveled from one side to the other. Indeed, because IMPs are stuck inside of the membrane, they cannot just glide through the central transport channel of the NPC as do free-floating molecules.

"Once Hoelz's team understood the structure of the NPC's linker-scaffold, they realized that it allows for the formation of little "gutters" around its outside edge that allow the IMPs to slip past the NPC from one side of the nuclear envelope to the other while always staying embedded in the membrane itself.

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"Taken together, the findings of the two papers represent a leap forward in scientists' understanding of how the human NPC is built and how it works. The team's discoveries open the door for much more research. "Having determined its structure, we can now focus on working out the molecular bases for the NPC's functions, such as how mRNA gets exported and the underlying causes for the many NPC-associated diseases with the goal of developing novel therapies," Hoelz says."

Comment: Everything works together in a coordinated fashion. It must do that all at once. It cannot be constructed bit by bit by evolution, because it won't work properly until it is complete. This is the very definition of irreducible complexity which requires a designing mind. Ingress an egress must tightly controlled always. When a molecule wants to enter it emits an alerting signal to trigerv the pore, and teh same at exiting. The signals can e chemical, electrical or physical force. All have been described. This is why the cells look lintelligent: the molecules follow intellgently designed signals. This can be only fully understood when the molecular architecture is found and its actions described.