Sure! Let's address **Question 1** in two steps, with explanations after each step, and a final answer at the end. --- ## **Question 1 (6 pts): Sequential Model of Allosteric Interactions** ### **Step 1: Drawing the Diagram and Labeling States** For a **dimeric receptor** (2 subunits), the **sequential** model (Koshland-Némethy-Filmer model) suggests that each subunit can change conformation independently, transitioning from T (tense, low-affinity) to R (relaxed, high-affinity) upon ligand binding. #### **Possible States:** - Both subunits in T state: TT - One subunit in T, one in R: TR or RT (but for a dimer, these are equivalent due to symmetry) - Both subunits in R state: RR #### **Diagram:** ```plaintext L TT <------> TR <------> RR L L ``` - TT: No ligand bound, both subunits in T - TR: One ligand bound, one subunit in T, one in R - RR: Two ligands bound, both subunits in R **Explanation:** This diagram shows the *stepwise* transition from TT to RR through the intermediate TR state, with ligand binding driving the conformational change in each subunit. --- ### **Step 2: Explaining Cooperativity and the Sequential Model** **Sequential Model Summary:** - Ligand binding induces a conformational change in one subunit at a time. - The binding of the first ligand makes the second binding event more favorable (positive cooperativity). - The diagram represents a pathway where each state is accessible, and the transition from TT to RR is not all-or-none. **Explanation:** The sequential model describes *graded* changes in affinity as each subunit binds ligand and adopts the R conformation. This allows for intermediate states and explains how partial cooperativity can occur, in contrast to the concerted (MWC) model, where all subunits switch states simultaneously. --- ### **Final Answer** **The diagram for a dimeric receptor under the sequential model is:** ```plaintext L TT <------> TR <------> RR L L ``` **This diagram and its labels describe how, in a sequential model, each subunit can independently change conformation upon ligand binding, leading to intermediate states and partial cooperativity. This results in a more gradual (sigmoidal) ligand binding curve compared to an all-or-none (concerted) model.** --- Would you like to proceed to Question 2?