Optimizing Transmembrane Protein Assemblies in Nanodiscs for Structural Studies: A Comprehensive Manual

Membrane protein structures offer a more accurate basis for understanding their functional correlates when derived from full-length proteins in their native lipid environment. Producing such samples has been a primary challenge in the field. Here, we present robust, step-by-step biochemical and biop...

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Main Authors: Fernando Vilela, Cécile Sauvanet, Armel Bezault, Niels Volkmann, Dorit Hanein
Format: Article
Language:English
Published: Bio-protocol LLC 2024-11-01
Series:Bio-Protocol
Online Access:https://bio-protocol.org/en/bpdetail?id=5099&type=0
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author Fernando Vilela
Cécile Sauvanet
Armel Bezault
Niels Volkmann
Dorit Hanein
author_facet Fernando Vilela
Cécile Sauvanet
Armel Bezault
Niels Volkmann
Dorit Hanein
author_sort Fernando Vilela
collection DOAJ
description Membrane protein structures offer a more accurate basis for understanding their functional correlates when derived from full-length proteins in their native lipid environment. Producing such samples has been a primary challenge in the field. Here, we present robust, step-by-step biochemical and biophysical protocols for generating monodisperse assemblies of full-length transmembrane proteins within lipidic environments. These protocols are particularly tailored for cases where the size and molecular weight of the proteins align closely with those of the lipid islands (nanodiscs). While designed for single-span bitopic membrane proteins, these protocols can be easily extended to proteins with multiple transmembrane domains. The insights presented have broad implications across diverse fields, including biophysics, structural biology, and cryogenic electron microscopy (cryo-EM) studies.
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institution OA Journals
issn 2331-8325
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publishDate 2024-11-01
publisher Bio-protocol LLC
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spelling doaj-art-ee11f11fdea44e73b5f222f2a99d36f12025-08-20T02:35:30ZengBio-protocol LLCBio-Protocol2331-83252024-11-01142110.21769/BioProtoc.5099Optimizing Transmembrane Protein Assemblies in Nanodiscs for Structural Studies: A Comprehensive ManualFernando Vilela0Cécile Sauvanet1Armel Bezault2Niels Volkmann3Dorit Hanein4Structural Studies of Macromolecular Machines in Cellulo Unit, Department of Structural Biology and Chemistry, Institut Pasteur, Université Paris Cité, CNRS UMR3528, Paris, FranceStructural Image Analysis Unit, Department of Structural Biology and Chemistry, Institut Pasteur, Université Paris Cité, CNRS UMR3528, Paris, FranceStructural Studies of Macromolecular Machines in Cellulo Unit, Department of Structural Biology and Chemistry, Institut Pasteur, Université Paris Cité, CNRS UMR3528, Paris, FranceStructural Image Analysis Unit, Department of Structural Biology and Chemistry, Institut Pasteur, Université Paris Cité, CNRS UMR3528, Paris, FranceStructural Studies of Macromolecular Machines in Cellulo Unit, Department of Structural Biology and Chemistry, Institut Pasteur, Université Paris Cité, CNRS UMR3528, Paris, FranceStructural Image Analysis Unit, Department of Structural Biology and Chemistry, Institut Pasteur, Université Paris Cité, CNRS UMR3528, Paris, FranceStructural Image Analysis Unit, Department of Structural Biology and Chemistry, Institut Pasteur, Université Paris Cité, CNRS UMR3528, Paris, FranceDepartment of Biological Engineering; Department of Electrical and Computer Engineering University of California, Santa Barbara, CA, USADepartment of Chemistry and Biochemistry, Department of Biological Engineering, University of California, Santa Barbara, CA, USAMembrane protein structures offer a more accurate basis for understanding their functional correlates when derived from full-length proteins in their native lipid environment. Producing such samples has been a primary challenge in the field. Here, we present robust, step-by-step biochemical and biophysical protocols for generating monodisperse assemblies of full-length transmembrane proteins within lipidic environments. These protocols are particularly tailored for cases where the size and molecular weight of the proteins align closely with those of the lipid islands (nanodiscs). While designed for single-span bitopic membrane proteins, these protocols can be easily extended to proteins with multiple transmembrane domains. The insights presented have broad implications across diverse fields, including biophysics, structural biology, and cryogenic electron microscopy (cryo-EM) studies.https://bio-protocol.org/en/bpdetail?id=5099&type=0
spellingShingle Fernando Vilela
Cécile Sauvanet
Armel Bezault
Niels Volkmann
Dorit Hanein
Optimizing Transmembrane Protein Assemblies in Nanodiscs for Structural Studies: A Comprehensive Manual
Bio-Protocol
title Optimizing Transmembrane Protein Assemblies in Nanodiscs for Structural Studies: A Comprehensive Manual
title_full Optimizing Transmembrane Protein Assemblies in Nanodiscs for Structural Studies: A Comprehensive Manual
title_fullStr Optimizing Transmembrane Protein Assemblies in Nanodiscs for Structural Studies: A Comprehensive Manual
title_full_unstemmed Optimizing Transmembrane Protein Assemblies in Nanodiscs for Structural Studies: A Comprehensive Manual
title_short Optimizing Transmembrane Protein Assemblies in Nanodiscs for Structural Studies: A Comprehensive Manual
title_sort optimizing transmembrane protein assemblies in nanodiscs for structural studies a comprehensive manual
url https://bio-protocol.org/en/bpdetail?id=5099&type=0
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AT armelbezault optimizingtransmembraneproteinassembliesinnanodiscsforstructuralstudiesacomprehensivemanual
AT nielsvolkmann optimizingtransmembraneproteinassembliesinnanodiscsforstructuralstudiesacomprehensivemanual
AT dorithanein optimizingtransmembraneproteinassembliesinnanodiscsforstructuralstudiesacomprehensivemanual