CHAPERONES AND MISFOLDED PROTEINS

Summary

This video explains the essential process of protein folding, highlighting the roles of molecular chaperones like HSP70 and HSP60, and the proteasome in maintaining protein quality. Proteins must fold into their correct three-dimensional structure to function properly, and chaperones help prevent misfolding by aiding in their correct configuration. Misfolded proteins, if not corrected, can lead to aggregation and disease. The proteasome is then tasked with degrading these problematic proteins. The video covers how these systems work together to ensure cellular health and prevent harmful protein accumulation.

Takeaways

• 😀 Proper protein folding is essential for a protein to become functional, and this process begins as the polypeptide emerges from the ribosome.
• 😀 Proteins fold into a three-dimensional structure and may require cofactors and modifications to perform their specific functions.
• 😀 The molten globule stage is the initial, flexible stage of folding where secondary structures like alpha-helices and beta-pleated sheets begin to form.
• 😀 Protein folding is a rapid process initially, but the fine-tuning of the tertiary structure can take several minutes and involves adjustments to side chains.
• 😀 Misfolded proteins are dangerous as they may aggregate and cause severe diseases due to exposed hydrophobic regions.
• 😀 Cells defend against misfolded proteins using molecular chaperones and proteasomes.
• 😀 Molecular chaperones help fold proteins correctly by binding to exposed hydrophobic patches and hydrolyzing ATP for mechanical work.
• 😀 Chaperones like HSP70 act early in the folding process, binding to polypeptide chains emerging from ribosomes to ensure proper folding.
• 😀 HSP60, another type of molecular chaperone, forms a large barrel structure where fully synthesized proteins can fold in a more controlled environment.
• 😀 Proteasomes, which are present throughout the cell, play a crucial role in degrading misfolded proteins through proteolysis, preventing them from accumulating.
• 😀 The efficiency of the chaperone system determines how much of a misfolded protein is degraded by the proteasome, emphasizing the importance of correct folding for protein survival.

Q & A

Why is protein folding important for cellular function?

Protein folding is crucial because it allows the polypeptide chain produced by ribosomes during translation to achieve a functional three-dimensional structure. This structure is essential for the protein's activity and ability to bind necessary cofactors or interact with other proteins.

What is the molten globule state in protein folding?

The molten globule is a flexible intermediate stage in protein folding that forms as the protein starts to fold. It contains secondary structural elements like alpha helices and beta-pleated sheets but is not yet in its final, functional form.

How long does it take for a protein to transition from the molten globule state to its correct tertiary structure?

The transition from the molten globule state to the correct tertiary structure typically takes several minutes, as this stage involves slower, more precise sidechain adjustments to finalize the protein's shape.

What happens to misfolded proteins?

Misfolded proteins are problematic because they can expose hydrophobic regions that cause them to aggregate. These aggregates can accumulate and lead to severe diseases, making their elimination crucial for cell health.

What are molecular chaperones and how do they help with protein folding?

Molecular chaperones are proteins that assist other proteins in folding correctly by binding to exposed hydrophobic patches on misfolded or incompletely folded proteins. They use the energy from ATP hydrolysis to ensure proper folding.

What is the role of the proteasome in protein quality control?

The proteasome is responsible for degrading misfolded or aberrant proteins through proteolysis. This process helps prevent the accumulation of dysfunctional proteins that could harm the cell.

What is the difference between HSP70 and HSP60 chaperones?

HSP70 acts early in the protein folding process, binding to emerging polypeptides and aiding in their initial folding steps. HSP60, on the other hand, is a chaperonin that forms a large barrel to isolate and provide a controlled environment for fully synthesized proteins to fold properly.

How does HSP70 assist in protein folding?

HSP70 binds to hydrophobic regions of polypeptides as they emerge from ribosomes, preventing misfolding. It requires several cycles of ATP hydrolysis to correctly fold the protein, with the help of co-chaperones like HSP40.

What happens when a protein remains misfolded for an extended period?

When a protein remains misfolded for too long, it becomes more likely to be targeted for degradation by the proteasome. Chaperones can continue to attempt folding, but if unsuccessful, the proteasome will degrade the protein.

How does ATP hydrolysis influence the function of chaperones like HSP60?

ATP hydrolysis plays a critical role in the function of chaperones like HSP60 by driving the folding process. When ATP binds to HSP60, it opens the chaperonin barrel, allowing the protein to unfold slightly and refold in a more favorable environment. The hydrolysis of ATP then facilitates the release of the protein if it is properly folded.