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Workshop / Seminar

AER/I Seminar with Cullen Greer

Zoom Only

About the event

Presenter: Cullen Greer

Group: Clowers

Title: Nanodisc Mimetics for Membrane Protein Mass Spectrometry

Abstract:  Proteins contained within the membrane of the eukaryotic cell are of significant interest for drug discovery, due to their varied functionality and external accessibility. Because of their amphiphilic nature, these structures are difficult to isolate from the membrane without significant denaturation of the native conformation, and as a result it is difficult to assess their biologically relevant characteristics ex vivo. A very sensitive analytical technique is often required due to the difficulty of extracting the native protein form. One suitable method, native (or nondenaturing) mass spectrometry, involves mimicking the environment of a bioanalyte inside the mass analyzer using a mimetic system that surrounds the protein in a similar fashion to the cell membrane. Lipoprotein nanodiscs are one such mimetic that sheathe a protein in a faux lipid bilayer, resulting in a stable complex that is of a tunable, monodisperse size. They make for an excellent compromise between denaturing mimetics and more native techniques that are not easily reproducible or necessarily resolvable, such as organic vesicles and liposomes. Recently, chargemodulating electrospray additives have been shown to consistently affect the stability of the membrane protein-nanodisc complex, enabling detection of the intact assemblage in addition to the released protein for a more holistic analysis. Additionally, nanodiscs of increasingly diverse lipid content are progressing towards a more native mimetic with wider protein applicability but result in increasingly convoluted mass spectra. Efforts in deconvolution of these data sets are advancing as well, indicating previously unexplored transmembrane proteins may soon be accommodated for study.

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Meeting ID: 991 5291 0987

Passcode: 125174

Date & Time: Apr 2, 2021 03:00 PM Pacific Time (US and Canada)