Seminar
Tuesday, November 21, 2017 - 12:00am
Graduate student Lucie Loftus will present
Using Nanodiscs to Determine the Structure of Membrane Proteins
on November 21, 2017 at 4:10 PM in Neville Hall, Room 3.
Abstract: Although membrane proteins (MPs) make up one-third of most proteomes, progress towards determining the three-dimensional structure of many MPs has been hindered by the lack of suitable membrane mimics. MP instability over time and issues with protein-lipid interactions in detergent-based environments have produced demand for a better membrane mimic1,2. Nanodiscs, the newest membrane mimic, have promised to provide a more relevant environment for the analysis of MPs. Nanodiscs are 8-16 nm discoidal-shaped lipid aggregates. In the center of the disc is a native-like lipid bilayer that is encircled by two membrane scaffold proteins (MSPs) that create the rim. The size of nanodiscs is determined by the length of the MSP, and the stoichiometry of lipids to MSP3,4. This seminar will focus on recent advances in nanodisc technology towards the goal of determining MP structures. The first study will examine the functionality of MPs from mammalian plasma membranes reconstituted into four studied nanodiscs5. The next study will look at the use of nanodiscs to determine the structure of the Cytb5-CytP450 complex by NMR spectroscopy6. The final study will examine the use of nanodiscs to determine the structure and ligand mechanisms of the TRPV1 ion channel by cyro-EM7. References: Zhang, M.; Huang, R.; Im, S.-C.; Waskell, L.; Ramamoorthy, A. J. Biol. Chem. 2015, 290 (20), 12705–12718. Zhou, H.-X.; Cross, T. A. Annu. Rev. Biophys. 2013, 42, 361–392. Bayburt, T. H.; Grinkova, Y. V.; Sligar, S. G. Nano Lett. 2002, 2 (8), 853–856. Denisov, I. G.; Grinkova, Y. V.; Lazarides, A. A.; Sligar, S. G. J. Am. Chem. Soc. 2004, 126 (11), 3477–3487. Roy, J.; Pondenis, H.; Fan, T. M.; Das, A. Biochemistry (Mosc.) 2015, 54 (41), 6299–6302. Zhang, M.; Huang, R.; Ackermann, R.; Im, S.-C.; Waskell, L.; Schwendeman, A.; Ramamoorthy, A. Angew. Chem. Int. Ed. 2016, 55 (14), 4497–4499. Gao, Y.; Cao, E.; Julius, D.; Cheng, Y. Nature 2016, 534 (7607), nature17964.