CryoEM reconstructions of membrane proteins solved in several amphipathic solvents, nanodisc, amphipol and detergents, yield amphipathic belts of similar sizes corresponding to a common ordered solvent layer

Zampieri, Veronica; Gobet, Alexia; Robert, Xavier; Falson, Pierre; Chaptal, Vincent

doi:10.1016/j.bbamem.2021.183693

Cited by 8 publications

(8 citation statements)

References 105 publications

(66 reference statements)

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“…Images of the model and of the associated map were taken, then slices at different density levels and thickness were selected to outline the lipids in different sites. The level at which the map is traced is indicated in the figure legends, according to [14] (see example in Figure 1A). Table 1 gives a list of all PDB and EMDB identifiers used in the figures, along with resolution, symmetry and associated literature reference.…”

Section: Methodsmentioning

confidence: 99%

“…In practice, very few deposited maps are normalised and no threshold can be considered universal. We used the contour level references introduced in the review published by Zampieri et al [14]. They use the density distribution profile that has a characteristic bell-like shape and identify four contour levels with 0 corresponding to the strongest density (where the ordered protein regions are visible), 1 to the level at which the ordered lipids are visible and the detergent/nanodisk density belt appears, and 2 is the level at which the detergent/nanodisk buoy is very visible.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Lipid-membrane protein interaction visualised by cryo-EM: A review

Biou

2023

Biochimica et Biophysica Acta (BBA) - Biomembranes

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Lipid-membrane protein interaction visualised by cryo-EM: A review

Biou

2023

Biochimica et Biophysica Acta (BBA) - Biomembranes

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“…While being essential for mechanistic studies and rational drug design, molecular structures for ion channels are more difficult to purify and crystallize than soluble proteins, mainly due to the necessity and difficulty of preserving the membrane-like environment. Detergents, amphipols, and nanodiscs have been commonly used to extract membrane proteins such as ion channels, and also serve as substitutes for the local membrane to stabilize the transmembrane domains ( Zampieri et al, 2021 ). In recent years, the single-particle cryo-EM technique has rapidly evolved as a powerful method for structure determination for various ion channels ( Martin et al, 2017 ; Basak et al, 2019 ; Dang et al, 2019 ; Masiulis et al, 2019 ; Zhao et al, 2019 ; Wang Q. et al, 2020 ; Sun and MacKinnon, 2020 ; Lin et al, 2021 ; Song et al, 2021 ; Yu et al, 2021 ).…”

Section: Computational Methods For Single-particle Cryo-emmentioning

confidence: 99%

“…Ion channels naturally reside in biological membranes which means preserving the amphiphilic local environment for the channel transmembrane domains is essential during cryo-EM sample preparation. Techniques such as nanodiscs can serve as good replacement for the membrane ( Zampieri et al, 2021 ). However, the disordered nature of these membrane memetics also add difficulties to the cryo-EM structural analysis.…”

Section: Computational Methods For Single-particle Cryo-emmentioning

confidence: 99%

Simulation and Machine Learning Methods for Ion-Channel Structure Determination, Mechanistic Studies and Drug Design

Zhu

Deng

Wang³

et al. 2022

Front. Pharmacol.

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Ion channels are expressed in almost all living cells, controlling the in-and-out communications, making them ideal drug targets, especially for central nervous system diseases. However, owing to their dynamic nature and the presence of a membrane environment, ion channels remain difficult targets for the past decades. Recent advancement in cryo-electron microscopy and computational methods has shed light on this issue. An explosion in high-resolution ion channel structures paved way for structure-based rational drug design and the state-of-the-art simulation and machine learning techniques dramatically improved the efficiency and effectiveness of computer-aided drug design. Here we present an overview of how simulation and machine learning-based methods fundamentally changed the ion channel-related drug design at different levels, as well as the emerging trends in the field.

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“…Proteins that are embedded in lipids in vivo (such as the spike protein or human membrane proteins) are often difficult to stabilize due their special hydrophobic parts, and various techniques to stabilize them by mutations or with detergents, amphipols, and nanodiscs are common. − …”

Section: Overview Of Spike Protein Structuresmentioning

confidence: 99%

Structure and Mutations of SARS-CoV-2 Spike Protein: A Focused Overview

Mehra

Kepp

2021

ACS Infect. Dis.

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The spike protein (S-protein) of SARS-CoV-2, the protein that enables the virus to infect human cells, is the basis for many vaccines and a hotspot of concerning virus evolution. Here, we discuss the outstanding progress in structural characterization of the S-protein and how these structures facilitate analysis of virus function and evolution. We emphasize the differences in reported structures and that analysis of structure–function relationships is sensitive to the structure used. We show that the average residue solvent exposure in nearly complete structures is a good descriptor of open vs closed conformation states. Because of structural heterogeneity of functionally important surface-exposed residues, we recommend using averages of a group of high-quality protein structures rather than a single structure before reaching conclusions on specific structure–function relationships. To illustrate these points, we analyze some significant chemical tendencies of prominent S-protein mutations in the context of the available structures. In the discussion of new variants, we emphasize the selectivity of binding to ACE2 vs prominent antibodies rather than simply the antibody escape or ACE2 affinity separately. We note that larger chemical changes, in particular increased electrostatic charge or side-chain volume of exposed surface residues, are recurring in mutations of concern, plausibly related to adaptation to the negative surface potential of human ACE2. We also find indications that the fixated mutations of the S-protein in the main variants are less destabilizing than would be expected on average, possibly pointing toward a selection pressure on the S-protein. The richness of available structures for all of these situations provides an enormously valuable basis for future research into these structure–function relationships.

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CryoEM reconstructions of membrane proteins solved in several amphipathic solvents, nanodisc, amphipol and detergents, yield amphipathic belts of similar sizes corresponding to a common ordered solvent layer

Cited by 8 publications

References 105 publications

Lipid-membrane protein interaction visualised by cryo-EM: A review

Lipid-membrane protein interaction visualised by cryo-EM: A review

Simulation and Machine Learning Methods for Ion-Channel Structure Determination, Mechanistic Studies and Drug Design

Structure and Mutations of SARS-CoV-2 Spike Protein: A Focused Overview

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