Mentors: Alison Bates, Ph.D., Carole Dabney-Smith, Ph.D., Gary A. Lorigan, Ph.D.

Nanodisc Interactions with KCNE4: Heart Kv Channel Modulator: KCNE4 (E4) is a protein and member of an accessory subunit family, which interacts with various voltage-gated potassium channels within the human body.  When the processes of these channels malfunction, numerous diseases can develop, such as: long QT syndrome, acute lymphoblastic leukemia, and allergic rhinitis.  E4 itself is known to inhibit potassium channels; however, the structure and dynamics of this protein before and after the interaction is largely unknown.  To explore conformational changes in E4 mutants, different membrane mimetics will be applied to E4, and any structural or dynamic changes will be observed with continuous-wave electron paramagnetic resonance (CW-EPR) spectroscopy.  Characterization of E4 within lipid vesicles and lipid nanoparticles will be done using dynamic light scattering (DLS).  In addition, the exploration of E4 within SMALP 300 will be used to investigate structural, dynamic, and incorporation differences with various mutants along the proposed E4 structure. This Styrene-Maleic Acid (SMA) derivative is one of many which were designed to overcome some of the difficulties with traditional SMA, such as lack of versatility to pH and divalent metals.  It has been shown through previous studies that SMA derivatives can produce similar structural and dynamic features to lipid vesicles.  As a result of this procedure, more information about the effects of membrane characteristics on the structure of E4 is hoped to be gained, potentially shedding more light on the inhibition of potassium channels by E4 within a biological system.

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