A Dynamical View of Membrane Transporter Function at Sub-Angstrom Resolution

Abstract

Membrane transporters provide the main mechanism for active exchange of materials between the cytoplasm and a cell's environment in a highly selective manner. These complex molecular machines present a structurally diverse group of pumps evolved to efficiently couple various sources of cellular energy to the selective transport of different molecules. Depending on the source of energy used and the type of the substrate transported, different protein architectures and, thus, different mechanisms are employed by membrane transporters. Active transporters undergo various degrees of protein conformational changes (induced, e.g., by ATP hydrolysis or by binding of the substrate and the co-transported ions) during their transport cycle. In other words, they adopt distinct conformational states during their function. Due to the difficulties associated with structure determination of membrane proteins, however, for the majority of structurally-known transporters only one of the major functional states has been structurally characterized. Substrate binding and translocation along the transport pathway in membrane transporters are closely coupled to numerous stepwise protein conformational changes of various magnitudes and forms that are induced by and/or coordinated with the energy-providing mechanisms. A detailed description of the mechanism of membrane transporters, therefore, relies on high-resolution methodologies that can describe the dynamics of the process at an atomic level. In this talk, latest results of molecular dynamics simulations performed on a number of membrane transporters with diverse mechanisms, and the molecular events involved in their function revealed by these simulations will be presented.