Final answer:
Mutations in the transmembrane region of proteins that mediate protein-ligand interactions can lead to an increase in dissociation constant (kd) and a potential decrease in the association constant (ka), thereby impacting the efficacy of ligand signaling.
Step-by-step explanation:
When evaluating the impact of mutations on the ka (association constant) and kd (dissociation constant) of a protein-ligand interaction, several scenarios can be hypothesized. A mutation in the transmembrane region of a protein like EGFR, which inhibits stabilization during dimerization post-ligand binding, would likely increase the kd due to reduced affinity between the receptor pairs, leading to a decrease in signal duration since the ligand-receptor complex is less stable. If the mutation affects an essential area for ligand recognition or binding sites, such as one that would normally recognize tetracycline, the ka could be reduced as the ability of the protein to bind the ligand is impaired, demonstrated by a higher K value in a binding affinity assay. If both mutations were present together, it can be expected that both ka and kd would be adversely affected, decreasing overall efficacy of the signaling cascade. Quantitative descriptions of binding affinities provide further support, as they show strong affinities correlate with multiple intermolecular bonds, implying that mutations disrupting these would have detrimental effects.