Final answer:
Amino acid substitutions within the CFTR protein, which can affect the formation of the α helix, may not always disrupt the protein's function. Mutations that preserve the hydrophobic core or do not interfere with critical bonds could be tolerated without causing cystic fibrosis. This is how individuals can have viable mutations within critical regions of the CFTR protein without exhibiting CF symptoms.
Step-by-step explanation:
The presence of amino acid substitutions in individuals without cystic fibrosis (CF) can be tolerated within the CFTR protein's α-helical structure due to the protein's structural flexibility and the possibility of redundant or compensatory mechanisms maintaining the channel's function. Amino acids within proteins, especially those in membrane-spanning regions such as α helices, are critical for proper folding and function. However, not all mutations have the same impact. Some substitutions may occur at positions where the specific side chain is not critical for maintaining the helical structure or the overall function of the protein.
For example, mutations that do not significantly alter the hydrophobicity of the core of the membrane-spanning helix or that do not disrupt key electrostatic or hydrogen bonds which stabilize the helix might be tolerated without loss of function. Additionally, the primary structure of a protein determines the basic assembly of amino acids, but proteins can accommodate certain changes without losing their ability to transport ions such as Cl⁻.
Understanding the nature of such mutations is important, as the dysfunctional proteins resulting from certain mutations lead to the symptoms of cystic fibrosis, which is caused by a malfunctioning CFTR ion channel. In people with CF, the CFTR gene mutation results in a defective protein that is not properly incorporated into the cell membrane and thus fails to transport Cl⁻ ions correctly.