Cellular intelligence: sending molecules to proper spots (Evolution)

by David Turell , Thursday, February 24, 2022, 19:28 (1001 days ago) @ David Turell

The cell is constantly producing proteins with different parts. Proper sorting to the correct destinations is controlled:

https://phys.org/news/2022-02-proteins-cell-team-decade-old-puzzle.html

"Researchers solve the more than 25-year-old puzzle of how proteins are sorted in the cell. A protein complex known as NAC (nascent polypeptide-associated complex) serves as a "gatekeeper" in protein synthesis, regulating the transport of proteins within the cell. The molecular mechanism behind this function has now been elucidated by cell and molecular biologists from Konstanz within an international collaborative project.

"For the maintenance of our cellular functions, it is essential that proteins are transported to various destinations within the cell—referred to as "cell organelles" in analogy to the organs of our body—while they are still being synthesized. But how is it possible to distinguish between different transport destinations and prevent proteins from reaching the wrong organelles? An international research team has now discovered how this complex process is controlled at the molecular level for an important cellular destination—the transport of nascent proteins to a membrane network of the cell, the endoplasmic reticulum.

"In their current publication in the journal Science, the researchers were able to show that a protein complex known among experts as NAC, which was discovered more than 25 years ago, plays a decisive role in this process: Like a gatekeeper, NAC ensures that only proteins with the endoplasmic reticulum as destination are passed on to the protein transporter SRP (signal recognition particle). SRP then mediates the transport of the "cargo" to the specified destination. If, on the other hand, a nascent protein has a destination other than the endoplasmic reticulum, the gatekeeper NAC denies access to the protein transporter SRP.

"Until now, it was known that two protein complexes, the aforementioned NAC and SRP, play an important role in the targeted transport of nascent proteins to the endoplasmic reticulum. SRP is the actual "transport protein" that establishes the contact of the nascent proteins together with the ribosome to the endoplasmic reticulum. It recognizes a specific transport signal that is encoded in the newly synthesized protein. However, there is a problem: SRP also binds non-specifically to ribosomes that have no signal for the endoplasmic reticulum.

"'Uncontrolled, SRP would bind to any ribosome close by and then transport it to the endoplasmic reticulum, regardless of whether or not a protein with that destination is currently being produced. This would result in countless misdeliveries that would severely impair the function and viability of the cell," explains Elke Deuerling,

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"According to this, NAC binds to the ribosome, specifically to the section where the nascent protein leaves the "protein factory." Like a gatekeeper, part of NAC sits protectively in front of this exit, the ribosomal tunnel, and denies SRP access to the ribosome and the nascent protein. Access is only granted when a transport signal sequence for the endoplasmic reticulum—encoded in the nascent protein—leaves the tunnel in the course of the protein synthesis. NAC recognizes this signal and changes its position on the ribosome. This way, the exit of the ribosomal tunnel becomes unblocked and SRP can now dock to the tunnel exit after being actively recruited to the ribosome via a "grabbing arm" of NAC, i.e. the UBA domain. After SRP binding and signal sequence transfer, the ribosome together with the nascent protein is transported to the endoplasmic reticulum.

"'Our study reveals the molecular function of NAC as a gatekeeper, granting SRP only access for those nascent proteins whose destination is the endoplasmic reticulum," Professor Elke Deuerling summarizes this fundamental control mechanism."

Comment: More evidence of necessary automaticity in cell functions. NAC is programmed to play its role, by design.