D1.2.18 Modification of polypeptides into their functional state (HL) Notes

Modification of Polypeptides into Their Functional State

1. The journey from a polypeptide to a functional proteinis a complex process that involves several modifications.
2. These changes are essential for the protein to achieve its final shape and function.

Why Are Modifications Necessary?

1. Functional Activation: Many polypeptides are inactive when first synthesized. Modifications activate them.
2. Stability and Longevity: Modifications can increase a protein’s stability, preventing degradation.
3. Specificity: Some modifications enable proteins to interact with specific molecules or perform specialized tasks.

Types of Modifications

1. Cleavage of Signal Peptides
   1. Many polypeptides have a signal peptideat one end, directing them to specific cellular locations.
   2. This peptide is often removed once the polypeptide reaches its destination.
2. Chemical Modifications
   1. Phosphorylation: Adding phosphate groups to amino acids like serine or threonine can activate or deactivate proteins.
   2. Glycosylation: Adding carbohydrate chains to proteins, often for cell recognition or stability.
   3. Methylation and Acetylation: Modifying amino acid side chains to alter protein function or interactions.
3. Folding and Stabilization
   1. Chaperone proteins assist in folding polypeptides into their correct shapes.
   2. Disulfide bonds form between cysteine residues, stabilizing the protein’s structure.
4. Formation of Quaternary Structures
   1. Some proteins consist of multiple polypeptide chains.
   2. These chains must assemble correctly to form the functional protein.
5. Conversion of Propeptides to Mature Peptides
   1. Inactive precursor proteins (propeptides) are often cleaved to produce active forms.

The Two-Stage Modification of Preproinsulin to Insulin

1. Insulin is a classic example of how polypeptides are modified to become functional proteins.
2. The process involves two main stages: