Membrane proteins control the movement of material and information in and out of cells, and thus play a central role in the flow and use of energy as well as the initiation of numerous signaling pathways. Additional accessory proteins are implicated in the trafficking and functional regulation of membrane proteins, thereby giving rise to highly organized “dynamic cellular networks” that originate at the molecular level from the operational attributes of component proteins. These protein complexes are working “molecular nano-machines” capable of specific and complex tasks. To understand how these molecular machines perform their functions, it is essential to understand their structure and dynamics. Membrane proteins are, of course, dynamic entities that perform a set of defined movements to execute their functions. Yet despite recent, sometimes spectacular progress, the quantitative study of membrane protein dynamics remains an immature area of research due to the limitations of techniques and theories used to study and interpret membrane protein dynamic behavior.
“We stand at the threshold of a second revolution in quantitative biology. With recent advances in membrane protein crystallization, structures are being obtained at an unprecedented rate. Spectroscopic, biophysical and modeling techniques have reached a level of applicability to complex systems unimaginable just a decade ago.” The Membrane Protein Structural Dynamics Consortium (MPSDC) is proposed as a highly interactive, tightly integrated and multidisciplinary effort focused on elucidating the relationship between structure, dynamics and function in a variety of membrane proteins. At a basic level, the main goal of this consortium is to decode the general mechanistic principles that relate function with protein movement and its associated fluctuation dynamics. These relationships are complex and any such understanding ultimately is based on atomic structures, for they represent the foundation from which functional and mechanistic insights must be framed in molecular terms. However, it is now abundantly clear that the linkage between structure and conformational dynamics is a major, and in some cases the dominant, influence on the behavior of biological systems. The next frontier is then to pioneer new technologies and approaches that elaborate the interplay between structure and its role in governing mechanism of operation. Knowledge of how these fundamental phenomena control membrane protein function will be required to understand the complex web of signaling and energy transduction mechanisms that define normal cellular physiology and pathophysiologic dysfunction.
MPSDC has been organized to acquire this fundamental knowledge. For some time, there has been an urgent, compelling need for high-resolution approaches to membrane protein structure and dynamics. However, we stand at the threshold of a second revolution in quantitative biology. With recent advances in membrane protein crystallization, structures are being obtained at an unprecedented rate. Spectroscopic, biophysical and modeling techniques have reached a level of applicability to complex systems unimaginable just a decade ago. Dynamic information must be accumulated to understand functional mechanism, and this requires the application of known strategies as well as method development. A tight integration between static structural methods, spectroscopic techniques, functional analyses and computational approaches will be essential to attack and solve these problems. A truly world class team has been assembled to carry out, in a highly collaborative and integrative way, the key experiments that will transform our fundamental understanding of the role protein dynamics play in linking structure and function.
Director and Principal Investigator
Department of Biochemistry and Molecular Biology and Institute for Biophysical Dynamics, The University of Chicago