The Trustees of Columbia University in the City of New York received a $323,941 Project Grant award from the National Institute of General Medical Sciences (NIGMS) Biomedical Research and Research Training program (CFDA 93.859) to elucidate how protein sequence controls the conformational dynamics of ATP-binding cassette (ABC) transporters, a class of molecular machines that use ATP hydrolysis to power the transport of diverse substrates across cell membranes. The research will leverage single-molecule fluorescence resonance energy transfer (smFRET) techniques to visualize the real-time translocation of individual substrate molecules and characterize the short-lived, high-energy intermediate conformations that drive the transport process. The study aims to reveal how specific packing interactions in the transmembrane domains and electrostatic interactions in the ATPase active site control the conformational landscape and functional trajectories of ABC transporters. This work will provide unprecedented mechanistic insights into how ATP hydrolysis can be leveraged by protein nanomachines to efficiently perform directed molecular-scale mechanical work.
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