Blind evolution is unable to build a functional and correctly folded protein. This requires complex protein machinery.
A functional protein? What does it mean? Here's a definition:
Functional proteins possess a biological activity and are involved in the biological function of a living organism.
Here's a list of the various proteins and protein complexes (often referred to as "protein machines") involved in the synthesis and proper folding of functional proteins:
1. Ribosome
- Function: The ribosome is the molecular machine responsible for translating mRNA into a polypeptide chain (a sequence of amino acids). It reads the mRNA sequence and assembles the corresponding amino acids into a polypeptide.
2. tRNA (Transfer RNA) and Aminoacyl-tRNA Synthetases
- tRNA: Transfers the appropriate amino acids to the ribosome per the mRNA's instructions.
- Aminoacyl-tRNA Synthetases: These enzymes attach the correct amino acid to its corresponding tRNA, ensuring the protein sequence is built accurately.
3. Elongation Factors (e.g., EF-Tu, EF-G)
- Function: These are proteins involved in the elongation phase of translation. They help with the accurate placement of tRNA in the ribosome and translocation of the ribosome along the mRNA.
4. Initiation Factors (e.g., IF1, IF2, IF3 in prokaryotes; eIFs in eukaryotes)
- Function: These proteins help assemble the ribosome on the mRNA to start translation. They ensure that translation begins at the correct start codon.
5. Release Factors (e.g., RF1, RF2 in prokaryotes; eRF in eukaryotes)
- Function: These proteins recognize the stop codon during translation and help release the completed polypeptide chain from the ribosome.
6. Chaperones
- Examples: Hsp70, Hsp90, GroEL/GroES, BiP, etc.
- Function: Chaperones are proteins that assist in the correct folding of newly synthesized polypeptides. They prevent misfolding and aggregation of proteins, often by binding to nascent chains and ensuring they fold into their correct conformations.
7. Chaperonins (e.g., GroEL/GroES in prokaryotes; TRiC/CCT in eukaryotes)
- Function: A specialized class of chaperones that provide an isolated environment for protein folding. GroEL/GroES form a complex that encapsulates the folding protein, preventing it from aggregating with other molecules.
8. Protein Disulfide Isomerases (PDI)
- Function: These enzymes catalyze the formation and rearrangement of disulfide bonds in proteins, which are important for the structural stability of many proteins.
9. Peptidyl-Prolyl Isomerases (PPIases)
- Function: These enzymes catalyze the cis-trans isomerization of peptide bonds at proline residues, which can be a rate-limiting step in protein folding.
10. Signal Recognition Particle (SRP) and SRP Receptor
- Function: For proteins destined for the secretory pathway, SRP recognizes the signal sequence of the emerging polypeptide and directs the ribosome to the endoplasmic reticulum (ER) membrane (in eukaryotes) or to the plasma membrane (in prokaryotes).
11. Sec61 Translocon
- Function: In the ER, the translocon is a protein-conducting channel that allows the nascent polypeptide to enter the ER lumen for further folding and modification.
12. Glycosyltransferases
- Function: These enzymes add carbohydrate groups to certain proteins, a process known as glycosylation, which is crucial for proper protein folding, stability, and function.
13. Proteasome and Ubiquitin-Proteasome System (UPS)
- Function: Misfolded proteins are recognized and tagged with ubiquitin, a small protein, which signals for their degradation by the proteasome. This system helps maintain protein quality control in the cell.
14. ER-Associated Degradation (ERAD) Proteins
- Function: A pathway within the ER that identifies misfolded proteins, retrotranslocates them to the cytosol, and targets them for degradation by the proteasome.
15. Protein Kinases and Phosphatases
- Function: These enzymes add or remove phosphate groups from proteins, respectively. Phosphorylation is a common post-translational modification that can influence protein folding, stability, and function.
16. Heat Shock Proteins (Hsps)
- Function: A subset of chaperones that are upregulated in response to stress, such as heat, to protect cells by ensuring proper protein folding or refolding and preventing aggregation.
17. Calnexin and Calreticulin
- Function: These are ER chaperones involved in the folding of glycoproteins and in the quality control process that ensures only properly folded proteins proceed along the secretory pathway.
18. Autophagy-Related Proteins (ATGs)
- Function: Autophagy is a process that can degrade and recycle misfolded or aggregated proteins. ATG proteins orchestrate the formation of autophagosomes that engulf defective proteins and organelles for lysosomal degradation.
As we can see, proteins don't form without protein machines. Each of these proteins and complexes plays a crucial role in ensuring that proteins are synthesized accurately and folded into their correct, functional conformations. Disruption in any part of this system can lead to protein misfolding, aggregation, and diseases such as Alzheimer's, Parkinson's, and cystic fibrosis.
The probability that a functional and correctly folded, very simple protein consisting of only 30 amino acids forms completely by chance is approximately 1 in 1.46×10^54. This means a mathematical impossibility. The prokaryotic ribosome (70S), found for example in bacteria, has about 55 different proteins. These proteins consist of a total of approximately 7,000–8,000 amino acids. The probability that the functional proteins of a prokaryotic ribosome would form randomly is extremely small, approximately 1 in 1.5×10^12653. This number is so small that it is practically zero.
