Predict the effect of exchanging a Ser for a pro in an -helical segment of a protein.
The correct answer and explanation is:
Exchanging serine (Ser) for proline (Pro) in an α-helical segment of a protein would likely disrupt the helical structure due to the distinct physicochemical properties of these amino acids.
Serine is a polar amino acid with a hydroxyl group (-OH) attached to its side chain. This group can form hydrogen bonds with the surrounding environment, contributing to stability in regions of the protein where hydrogen bonding is crucial. Serine’s smaller, flexible side chain allows for ease of rotation and accommodation within the tightly packed α-helix, without significantly disrupting the helical backbone.
On the other hand, proline is a unique amino acid with a cyclic side chain that bonds back to the nitrogen atom of the amino acid’s backbone. This creates a rigid, constrained structure that severely limits the ability of proline to participate in regular hydrogen bonding, which is a key feature for maintaining the α-helix. Proline’s incorporation into the α-helix leads to a “kink” or break in the helix because it cannot adopt the same angle as the other amino acids, which are more flexible. This distortion can destabilize the helical conformation, making it less favorable for the protein’s overall structure.
Therefore, exchanging Ser for Pro in an α-helical region is likely to disrupt the helical structure, leading to a local destabilization. The α-helix could unfold or adopt an alternative secondary structure, depending on the context of the surrounding residues. This change can also affect the protein’s overall folding and its biological function, especially if the helix is crucial for maintaining the protein’s active site or interacting with other molecules. In some cases, however, proline might induce a useful structural feature like a turn or loop, but its effect on an α-helix is generally disruptive.