U01.01.018 Posttranslational modifications

Protein synthesis is just the first act in the protein drama. Newly minted proteins often undergo a series of modifications after their creation on the ribosome. These adjustments, known as posttranslational modifications (PTMs), are like the finishing touches on a masterpiece, shaping the protein’s final form and function. Let’s delve into the world of PTMs for Step 1 of the USMLE:

1. Trimming the Excess: Shedding Signal Sequences

Imagine a protein with an extra tag. Sometimes, newly synthesized proteins have additional sequences (propeptides) that need to be removed for proper function. These propeptides act like tags that guide the protein to its initial destination.

Example: Trypsinogen, an inactive precursor enzyme in the pancreas, has a propeptide. This propeptide gets snipped off, transforming trypsinogen into the active enzyme trypsin. This trimming ensures trypsin doesn’t prematurely activate within the pancreas, preventing unwanted tissue damage.

2. Chemical Makeovers: Covalent Alterations

Proteins can undergo various chemical modifications that significantly impact their properties, like adding functional groups or changing their electrical charge. Here are some key PTMs:

Phosphorylation: This is a superstar PTM, involving the attachment of a phosphate group by enzymes called kinases. Phosphorylation can activate or deactivate enzymes, regulate protein-protein interactions, and influence where a protein resides within the cell.
Glycosylation: Sugars can be attached to proteins, affecting their stability, folding, targeting to specific locations, and interactions with other cells. Imagine adding sugar decorations to a protein, changing how it interacts with its surroundings.
Hydroxylation, methylation, acetylation: These modifications can influence protein folding, stability, and interactions with other molecules. Think of them as fine-tuning adjustments that optimize protein function.
Ubiquitination: This PTM involves attaching a molecule called ubiquitin, which acts like a red flag for protein degradation. Proteins tagged with ubiquitin are targeted for destruction by the proteasome, a cellular “recycling center” that breaks down unneeded proteins.

3. Protein Folding Helpers: Chaperone Proteins

Proteins need to fold into specific shapes to function correctly. Chaperone proteins act like molecular chaperones, assisting other proteins in folding properly and preventing misfolding. Imagine chaperones as protein-folding instructors, guiding polypeptides to their final structure.

Heat Shock Proteins: A specific type of chaperone, like HSP60 in yeast, gets particularly active at high temperatures. They help prevent protein denaturation (unfolding) caused by heat stress, ensuring proteins maintain their proper shape.

Key Takeaways for Step 1:

PTMs are chemical alterations that occur after protein synthesis, significantly impacting protein function.
Common PTMs include phosphorylation, glycosylation, and ubiquitination.
Chaperone proteins assist with proper protein folding and prevent misfolding.

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U01.01.018 Posttranslational modifications

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