Structure-relaxation mechanism for the response of T4 lysozyme cavity mutants to hydrostatic pressure

High pressure has emerged as a powerful tool for exploring the energy landscape of proteins, but structural origins of the pressure response remain controversial. The results of this study on a cavity mutant of T4 lysozyme (L99A) provide direct evidence for a structure-relaxation mechanism wherein pressure shifts conformational equilibria toward states with alternative packing arrangements that fill cavities or voids in the core. Both structure relaxation and cavity hydration can occur in response to pressure, and which dominates is found to depend on details of the energy landscape. The results also address conflicting views regarding the pressure response of L99A that have recently been published.