What Happens to Faulty Protiens?

Summarized by Jeannine Yu

A protein is a type of macromolecule commonly found within cells. In order for the human body to be able to function properly, it is important that our cells are able to produce proteins for use in cell structure, cell creation, biochemical reactions, etc. Proteins are made up of building blocks called amino acids, which exist in 20 different forms. When amino acids are linked together, they are called polypeptides, which are proteins. This linking of amino acids is crucial for human survival and mistakes can often lead to issues with faulty proteins that do not function properly.

In order for amino acids to be linked, the protein synthesis process must ensue. First, there is a part of the cell called the ribosome which oversees the production of proteins. Here, there is mRNA, which is a type of genetic material—similar to instructions or a blueprint for making the proteins. On the mRNA, there are codons, which are specific groups of 3 nucleotides (building blocks of DNA, the human genetic material). There are 5 types of nucleotides: Adenosine (A), Thymine (T), Uracil (U), Cytosine (C), and Guanine (G). Each codon on the mRNA is like a set of instructions or like an encrypted code. For example, one codon may look like “AGU.” These nucleotides always have an opposite nucleotide—Adenosine and Thymine/Uracil or Cytosine and Guanine are opposite pairs. During protein synthesis, codons are paired with anticodons, which are the codons with opposite nucleotides with respect to the nucleotides in the original codon. For example, if the codon was “AGU,” then the anticodon would be “UCA.”

Image Courtesy of Khan Academy, Lesson 3: Transcription and RNA processing, https://www.khanacademy.org/science/ap-biology/gene-expression-and-regulation/transcription-and-rna-processing/a/overview-of-transcription

Once these codons are paired together, the amino acid is connected to the polypeptide and once all the codons have been “scanned,” the process is over. However, sometimes this process can result in errors. Although ribosomes originally were considered done with protein synthesis after this point, new research has shown that they have additional mechanisms for spotting the errors in creating proteins.

In multiple experiments, it was shown that the average rate of occurrence of these errors is 1 per 20,000 amino acids, but the actual number varies in other studies. During this study on the AAU codon (which was commonly mistakenly translated into lysine instead of asparagine), it was seen that after a mistake was made in the protein creation process, the ribosome slowed in protein creation and even released the polypeptide sooner than expected.

There are 3 main sites where binding of amino acids occurs on the codons: the A site, P site, and T site. The A site is the beginning site and the T site is the end site. The anticodons are originally brought to the A site, but then it shifts to the P site, opening room for the next anticodon to be brought to the A site. The cycle finishes when the first anticodon reaches the T site. Through experimentation, it was shown that errors in putting down the right anticodon led to a greater rate of further errors, such as additional mismatches. The reasoning for this phenomenon is unknown, but it is suspected that codons may momentarily be in the A site together, leading to more mismatches created. Another observation was that polypeptides were more likely to finish being translated earlier once a mistake has been made. Although the exact reasoning for this is still unclear, the best answer is that the mismatched protein creates signals within the ribosome that send the message to stop creating the protein. The factors that are giving the “go” signal to the ribosome suddenly know to stop production.

Boumphreyfr vector conversion by Glrx, CC BY-SA 3.0 https://creativecommons.org/licenses/by-sa/3.0, via Wikimedia Commons

Regardless of how exactly cells are able to stop protein production after mistakes, this research has shown that cells do have alternate mechanisms past protein synthesis itself that help to prevent faulty proteins from becoming an issue, demonstrating the complexity of human life.

References:

Ajinomoto, 20 Amino Acids That Make Up Proteins, Date Accessed: 9-5-2023, https://www.ajinomoto.com/amino-acids/20-amino-acids#:~:text=acids%E2%80%94research%20serendipity-,Types%20of%20All%20Amino%20Acids,up%20the%2020%20amino%20acids