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Klöpfer, K. ; Hagn, F.

Beyond detergent micelles: The advantages and applications of non-micellar and lipid-based membrane mimetics for solution-state NMR.

Prog. Nucl. Magn. Reson. Spectrosc. 114-115, 271-283 (2019)
Postprint DOI
Open Access Green
Membrane proteins are important players in signal transduction and the exchange of metabolites within or between cells. Thus, this protein class is the target of around 60 % of currently marketed drugs, emphasizing their essential biological role. Besides functional assays, structural and dynamical investigations on this protein class are crucial to fully understanding their functionality. Even though X-ray crystallography and electron microscopy are the main methods to determine structures of membrane proteins and their complexes, NMR spectroscopy can contribute essential information on systems that (a) do not crystallize and (b) are too small for EM. Furthermore, NMR is a versatile tool for monitoring functional dynamics of biomolecules at various time scales. A crucial aspect of such studies is the use of a membrane mimetic that resembles a native environment and thus enables the extraction of functional insights. In recent decades, the membrane protein NMR community has moved from rather harsh detergents to membrane systems having more native-like properties. In particular, most recently phospholipid nanodiscs have been developed and optimized mainly for solution-state NMR but are now also being used for solid-state NMR spectroscopy. Nanodiscs consist of a patch of a planar lipid bilayer that is encircled by different (bio-) polymers to form particles of defined and tunable size. In this review, we provide an overview of available membrane mimetics, including nanodiscs, amphipols and bicelles, that are suitable for high-resolution NMR spectroscopy and describe how these advanced membrane mimetics can facilitate NMR studies on the structure and dynamics of membrane proteins. Since the stability of membrane proteins depends critically on the chosen membrane mimetic, we emphasize the importance of a suitable system that is not necessarily developed for solution-state NMR applications and hence requires optimization for each membrane protein. However, lipid-based membrane mimetics offer the possibility of performing NMR experiments at elevated temperatures and studying ligand and partner protein complexes as well as their functional dynamics in a realistic membrane environment. In order to be able to make an informed decision during the selection of a suitable membrane system, we provide a detailed overview of the available options for various membrane protein classes and thereby facilitate this often-difficult selection process for a broad range of desired NMR applications. (C) 2019 Elsevier B.V. All rights reserved.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Review
Korrespondenzautor
Schlagwörter Lipids ; Membrane Proteins ; Nanodiscs ; Nmr ; Structure; Phospholipid-bilayer Nanodiscs; Resolution Structure Determination; Synthetic Peptide Analogs; Apolipoprotein-a-i; Solid-state; Protein Structure; Amphipathic Polymers; Density-lipoprotein; Crystal-structures; Amphipols
ISSN (print) / ISBN 0079-6565
e-ISSN 1873-3301
Zeitschrift Progress in Nuclear Magnetic Resonance Spectroscopy
Quellenangaben Band: 114-115, Heft: , Seiten: 271-283 Artikelnummer: , Supplement: ,
Verlag Elsevier
Verlagsort Oxford
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Structural Biology (STB)