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New Native Nanodiscs for Membrane-Protein Biophysics

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Biophysical Seminar by Prof. Sandro Keller on "New Native Nanodiscs for Membrane-Protein Biophysics"

Nanodiscs that harbour individual membrane proteins or membrane-protein complexes in a lipid-bilayer environment hold great promise for biophysical investigations under well-controlled yet native-like conditions. Our laboratory focusses on new methods for the direct, detergent-free ex-traction of proteins from cellular membranes into native nanodiscs, which preserve both the over-all bilayer architecture and the local lipid composition of the original cellular membrane. Thus, these native nanodiscs render membrane proteins amenable to in vitro biophysical investigations without ever removing the proteins from a lipid-bilayer environment. Recently, we have developed and used novel amphiphilic polymers with improved properties for forming nanodiscs that are compatible with a broad range of ensemble and single-molecule biophysical techniques.[1–3] In this talk, I will present selected examples including antibody–receptor and peptide–lipid interactions studied by microfluidic diffusional sizing, membrane-protein complexes investigated by mass spec-trometry, and cell-free translation of membrane proteins with cotranslational insertion into lipid-bilayer nanodiscs.


[1] D. Glück, A. Grethen, M. Das, O.P. Mmeka, E. Pérez Patallo, A. Meister, R. Rajender, S. Kins, M. Räschle, J. Victor, C. Chu, M. Etzkorn, Z. Köck, F. Bernhard, J.O. Babalola, C. Vargas, S. Keller. Electroneutral polymer nanodiscs enable interference-free probing of membrane proteins in a lipid-bilayer environment. Small 2022, accepted

[2] B. Danielczak, M. Rasche, J. Lenz, E. Pérez Patallo, S. Weyrauch, F. Mahler, M.T. Agbadaola, A. Meister, J.O. Babalola, C. Vargas, C. Kolar, S. Keller. A bioinspired glycopolymer for capturing membrane proteins in native-like lipid-bilayer nanodiscs. Nanoscale 2022, 5, 1855

[3] F. Mahler, A. Meister, C. Vargas, G. Durand, S. Keller. Self-assembly of protein-containing lipid-bilayer nanodiscs from small-molecule amphiphiles. Small 2021, 17, 2103603

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