Question

How many disulfide bonds are formed in proinsulin after removal of the signal sequence of preproinsulin?

• A. Four
• B. Three
• C. Two
• D. One

Hint:

The three disulfide bonds (two interchain and one intrachain) are established during the proinsulin stage and are preserved intact during its proteolytic cleavage into mature insulin.

Answer 1

The Correct Option is B

Step 1: Understanding the Concept:
Insulin is a peptide hormone synthesized in the pancreatic $\beta$-cells.
It is initially translated as a precursor molecule called preproinsulin, which contains an N-terminal signal peptide that directs the nascent chain to the rough endoplasmic reticulum (RER).
In the RER, the signal peptide is cleaved by signal peptidase to yield proinsulin.

Step 2: Detailed Explanation:
Proinsulin is a single polypeptide chain containing the A and B chains of mature insulin connected by a linker peptide called the C-peptide (connecting peptide).
Inside the lumen of the endoplasmic reticulum, the proinsulin polypeptide chain undergoes folding.
The folding process positions specific cysteine residues close to each other, allowing the formation of three highly stable disulfide bonds.
These disulfide bonds are crucial for establishing the correct tertiary structure of the hormone.
Two of these are interchain disulfide bonds that link the A and B chains together:
The first interchain bond forms between Cys-A7 and Cys-B
The second interchain bond forms between Cys-A20 and Cys-B
The third is an intrachain disulfide bond located entirely within the A chain, connecting Cys-A6 and Cys-A
Following the formation of these three disulfide bonds, proinsulin is transported to the Golgi apparatus and packaged into secretory granules.
Inside these granules, prohormone convertases cleave the C-peptide, releasing the mature active insulin molecule.
This mature insulin retains the exact same three disulfide bonds established in the proinsulin phase.

Step 3: Final Answer:
Therefore, there are exactly three disulfide bonds formed in proinsulin.