Speaker: Gerhard Wagner, Professor, Biological Chemistry and Molecular Pharmacology, Harvard Medical School
Title: Characterizing membrane proteins in native membranes without tricks
Abstract: Structural and functional studies of membrane proteins require the membrane proteins be placed in membrane mimicking environments. Often this is pursued by using detergent micelles, and stable complexes are obtained by cross-linking and/or adding antibodies or nanobodies. More recently, phospholipid nanodiscs have been employed as better membrane surrogates. We have designed covalently circularized nanodiscs (cNDs) that can provide stable environments for studies of membrane proteins and their complexes with soluble proteins. We have used NMR, cryoEM and other biophysical methods to study the neurotensin receptor NTR1 in complex with the heterotrimeric G protein Gi in a covalently circularized nanodisc. No crosslinking, antibodies or nanobodies were used as complex stability was obtained by the placement in cNDs. We are using nanodiscs also for other small membrane proteins in complexes with soluble proteins.
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