April 25, 2024: Lan Guan & Hariharan Parameswaran, Texas Tech University Health Sciences Center

CryoEM revealed a high-energy state of a 53-kDa membrane transporter trapped by a conformation-specific nanobody
Cation-coupled transporters play critical roles in many aspects of cell physiology and pharmacokinetics. They are current drug targets and are involved in many diseases, including cancers, metabolic diseases, and neurodegenerative diseases. Molecular analyses of those membrane-embedded transporters are technically challenging due to their intrinsic hydrophobicity and protein flexibility required to conduct their functions. Many 3-D structures of membrane transporters are available to date; however, many details regarding transport mechanisms are still elusive. In this presentation, Professor Lan Guan and Research Assistant Professor Hariharan Parameswaran will share their recent achievements in advancing the knowledge of membrane transport mechanisms. They will highlight the use of conformation-specific nanobodies to isolate the high-energy state and the use of the fiducial NabFab to overcome the size limitation of a small sugar transporter for cryoEM analysis. Hydrogen/deuterium exchange-mass spectrometry and isothermal titration calorimetry were used to determine the functional state of this cryoEM structure.