Chapter 6, Problem 15P

Answers to all problems are at the end of this book. Detailed solutions are available in the Student Solutions Manual, Study Guide, and Problems Book.

(Research Problem) The Nature of Protein-Protein Interactions How do proteins interact? When one protein binds to another, one or both changes conformation. Two hypotheses have been proposed to describe such binding: In the induced fit model, the interaction between a protein and a ligand induces a conformation change (in the protein or ligand) through a step wise process. In the conformational selection model, the

unliganded protein (in the absence of the ligand) exists as an ensemble of conformations in a dynamic equilibrium. The binding ligand interacts preferentially with one among many of these conformations and shifts the equilibrium in favor of the selected conformation. Three recent papers shed light on this question:

Boehr, D.. and Wright, P. E._, 2008. How do proteins interact? Science 320:1429-1430.

Gsponer, J.. et al., 200&. A coupled equilibrium shift mechanism in calmodulin-mediated signal transduction. Structure 16:736—'746.

Lange, O., et al., 2008. Recognition dynamics up to microseconds revealed from an R DC-derived ubiquitin ensemble in solution. Science 320:1471-1475.

Consult these papers and answer the following questions:

What proteins were studied in these papers?

What techniques were used, and what time scales of protein motion were studied?

What were the conclusions of these papers, and how do these results illuminate the choice between induced fit and conformational selection in protein-protein interactions?