New Insight into the Cell’s Quality-Control Systems Provided Added Evidence for Design
Have you ever had trash that the garbage man wouldn’t take? We sure have.
I remember a few years ago we re-carpeted the upstairs of our home. Instead of having the carpet layers take the left over remnants with them when they finished the job, we decided to save the carpet scraps—just in case. Big mistake!
After spending several months tripping over the rolls of carpet in our garage, we decided to throw them away. First, we naively dragged the carpet to the curb and set it next to our trash barrels. The trash men refused to take it. The next week, we took great pains to fit the carpet into the appropriate trash barrel, only to have it removed by the trash collectors and left unceremoniously on the curbside. I don’t remember how we finally got rid of the carpet, but I do remember the valuable lesson we learned about trash disposal and what the garbage man will and won’t take.
Cells face similar problems when it comes to disposing biochemical trash. Some cellular garbage is readily cleared from the cell. Other biomolecular refuse, like carpet remnants, is difficult for the cell’s machinery to process. This difficulty causes biochemical waste to accumulate in the cell’s interior.
Accumulating cellular garbage is not a matter of inconvenience, like the unwanted carpet stacked in my garage. It’s a real concern. In fact, part of the etiology of some neurodegenerative disorders, like Huntington’s Disease, involves the build-up of aggregates formed from protein waste.
Understandably, biologists are interested in trying to learn how and why protein waste accumulates in cells and what can be done to eliminate it. New work published in Nature provides important insight into how protein waste is processed by the cell. This new knowledge suggests a possible strategy to help cells clear out intractable biomolecular garbage. This new understanding also adds to the evidence that life stems from a Creator’s hand.
Next week I’ll discuss these ideas. This week I’ll describe what makes up a major part of the cell’s garbage and the central cogs in the cell’s waste disposal machinery.
The cell’s waste, like most garbage, doesn’t start out that way. Initially, it is useful. Much of the offending cellular rubbish consists of protein aggregates. Proteins are chain-like molecules that fold into precise three-dimensional structures. A protein’s three-dimensional architecture determines its function. Proteins play a key role in virtually every cellular function and help form nearly every cellular structure.
Proteins form when the cellular machinery links together, in a head-to-tail fashion, smaller subunit molecules called amino acids. The amino acids that make up the cell’s protein chains possess a variety of chemical and physical properties. Each amino acid sequence imparts the protein with a unique chemical and physical profile along its chain. This profile determines how the protein folds, and therefore, how it interacts with other protein chains to form functional protein complexes. The amino acid sequence of a protein ultimately determines its function, since the amino acid sequence determines the protein’s structure, and hence, structure dictates function.
Cells constantly make and destroy proteins. Proteins that take part only in highly specialized activities within the cell are manufactured only when needed. Once these proteins outlive their usefulness, the cell breaks them down into their constitutive amino acids. The removal of unnecessary proteins helps keep the cell’s interior free of clutter. And the amino acids can be used to build new proteins.
On the other hand, proteins that play a central role in the cell’s operation are produced on a continual basis. After a period of time, however, these proteins inevitably suffer damage from wear and tear and must be destroyed and replaced with newly made proteins. It’s dangerous for the cell to let damaged proteins linger. Once a protein is damaged, it’s prone to aggregate with other proteins. These aggregates disrupt cellular activities.
Another source of protein waste is faulty manufacturing. The assembly of protein chains from constitutive amino acids occurs with a high degree of fidelity. However, the folding of the protein chains into their native three-dimensional architecture is still error-prone. The error rate is typically about thirty percent. (As I point out in The Cell’s Design and elsewhere, this high error rate represents an elegant design strategy to ward off viruses.)
Misfolded proteins can cause profound problems for the cell. The negative consequences of their presence extend beyond loss of function for the misfolded protein. Improperly folded proteins have a global impact on cellular health. These deformed proteins tend to form aggregates inside the cell, fouling up its inner workings.
Fortunately, the cell possesses protein degradation machinery that clears unneeded, damaged, and improperly manufactured proteins.
Protein degradation is a complex undertaking that begins with what biochemists call ubiquitination. When damaged, proteins misfold adopting a nonnatural three-dimensional shape. Misfolding exposes amino acids in the damaged protein’s interior. These exposed amino acids are recognized by an enzyme called E3 ubiquitin ligase, which attaches a small protein molecule called ubiquitin to the damaged protein.
Ubiquitin functions as a molecular tag, informing the cell’s machinery that the damaged protein is to be destroyed. Severely damaged proteins will receive multiple ubiquitin tags. Ubiquitination is reversible by deubiquitinating enzymes removing the ubquitin labels. This deubiquitinating activity prevents the cell’s machinery from breaking down fully functional proteins that may have been accidentally tagged for destruction.
A massive protein complex called a proteasome destroys damaged, ubiquitinated proteins. The overall molecular architecture of the proteasome consists of a hollow cylinder topped with a lid that can exist in either an opened or closed conformation. Protein breakdown takes place within the cylinder’s interior. The lid portion of the proteasome controls the entry of ubiquitinated proteins into the cylinder.
As I point out in The Cell’s Design, the proteasome lid contains deubiquitinating activity. If a protein has only one or two ubiquitin tags, it’s likely not damaged and the lid will remove the tags thereby rescuing the protein from destruction. The cell’s machinery will recycle the rescued protein. If, on the other hand, the protein has several ubiquitin tags, the lid cannot remove them all and shuttles the damaged protein entry into the proteasome cylinder.
The proteasome lid regulates a delicate balance between destruction and rescue, ensuring that truly damaged proteins are destroyed and salvageable proteins escape unnecessary degradation. As I argue in The Cell’s Design, the cell’s protein degradation system displays fine-tuning and also elegant biochemical logic that points to a Creator’s handiwork.
High-precision equates with the best possible quality in engineered systems. Precision and fine-tuning do not arise by happenstance in either art or engineering. Rather, they come about only as a result of careful planning and a commitment to execute designs using the best craftsmanship possible. This makes fine-tuning and precision clear indicators of human intelligent design. And, by analogy, makes the molecular precision and fine-tuning that pervades the design of biochemical systems potent markers for the work of a Divine Engineer.
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