Final Report Summary - PROTDYN2FUNCTION (Functional protein dynamics studied by solution- and solid-state NMR spectroscopy)
Proteins are dynamic machineries which fulfill their actions by adopting multiple conformational states in a dynamic manner. This project aimed at developing and applying NMR methods as well as other biophysical, computational and biochemical methods to delineate the link between protein motions and function. In terms of new methods, we have developed in particular solid-state NMR measurements which allow detecting transient short-lived conformations of proteins. Furthermore, we have developed methods for structure determination that combine NMR data with cryo-EM data, which enabled us to determine the structure of almost 0.5 MDa-large enzyme complex.
In terms of applications, we have characterized chaperones and membrane proteins. Chaperones are “helper proteins” which assist poorly soluble/aggregation-prone/misfolded protein in remaining in solution or refolding. We have provided insight into a large (ca. 1 MDa) chaperone of the Hsp60 family, its conformational states, its interaction with unfolded proteins, and its ATP-driven large-scale rearrangements. Furthermore we have provided detailed insight into the mechanisms by which highly aggregation-prone mitochondrial membrane proteins are transported across the mitochondrial inter-membrane space. Lastly, we have studied the dynamics and interactions of membrane proteins in detergent, and how detergents alter membrane protein structure.
Taken together, this project has gone from the development of advanced NMR methods and integration of various methods, to challenging biological questions, particularly in the chaperone field.
In terms of applications, we have characterized chaperones and membrane proteins. Chaperones are “helper proteins” which assist poorly soluble/aggregation-prone/misfolded protein in remaining in solution or refolding. We have provided insight into a large (ca. 1 MDa) chaperone of the Hsp60 family, its conformational states, its interaction with unfolded proteins, and its ATP-driven large-scale rearrangements. Furthermore we have provided detailed insight into the mechanisms by which highly aggregation-prone mitochondrial membrane proteins are transported across the mitochondrial inter-membrane space. Lastly, we have studied the dynamics and interactions of membrane proteins in detergent, and how detergents alter membrane protein structure.
Taken together, this project has gone from the development of advanced NMR methods and integration of various methods, to challenging biological questions, particularly in the chaperone field.