Neutrons to Study the Structure and Dynamics of Membrane Proteins

Wood, Kathleen; Zaccaı̈, Giuseppe

doi:10.1002/9783527621224.ch9

Cited by 2 publications

(1 citation statement)

References 48 publications

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“…Another classical method for elucidating the structural and dynamic changes that happens during lipid protein interaction include neutron scattering techniques such as inelastic and quasielastic neutron scattering (Swenson et al, 2008;Wood and Zaccai, 2008;Armstrong et al, 2012) as well as neutron spin echo (Kumarage et al, 2021). The quasielastic neutron scattering data can be converted to the dynamic nature of lipid membranes based on scattering laws (Qian et al, 2020).…”

Section: Neutron Scattering Studiesmentioning

confidence: 99%

Pore Forming Protein Induced Biomembrane Reorganization and Dynamics: A Focused Review

Ponmalar

Sarangi

Basu

et al. 2021

Front. Mol. Biosci.

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Pore forming proteins are a broad class of pathogenic proteins secreted by organisms as virulence factors due to their ability to form pores on the target cell membrane. Bacterial pore forming toxins (PFTs) belong to a subclass of pore forming proteins widely implicated in bacterial infections. Although the action of PFTs on target cells have been widely investigated, the underlying membrane response of lipids during membrane binding and pore formation has received less attention. With the advent of superresolution microscopy as well as the ability to carry out molecular dynamics (MD) simulations of the large protein membrane assemblies, novel microscopic insights on the pore forming mechanism have emerged over the last decade. In this review, we focus primarily on results collated in our laboratory which probe dynamic lipid reorganization induced in the plasma membrane during various stages of pore formation by two archetypal bacterial PFTs, cytolysin A (ClyA), an α-toxin and listeriolysin O (LLO), a β-toxin. The extent of lipid perturbation is dependent on both the secondary structure of the membrane inserted motifs of pore complex as well as the topological variations of the pore complex. Using confocal and superresolution stimulated emission depletion (STED) fluorescence correlation spectroscopy (FCS) and MD simulations, lipid diffusion, cholesterol reorganization and deviations from Brownian diffusion are correlated with the oligomeric state of the membrane bound protein as well as the underlying membrane composition. Deviations from free diffusion are typically observed at length scales below ∼130 nm to reveal the presence of local dynamical heterogeneities that emerge at the nanoscale—driven in part by preferential protein binding to cholesterol and domains present in the lipid membrane. Interrogating the lipid dynamics at the nanoscale allows us further differentiate between binding and pore formation of β- and α-PFTs to specific domains in the membrane. The molecular insights gained from the intricate coupling that occurs between proteins and membrane lipids and receptors during pore formation are expected to improve our understanding of the virulent action of PFTs.

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Section: Neutron Scattering Studiesmentioning

confidence: 99%

Pore Forming Protein Induced Biomembrane Reorganization and Dynamics: A Focused Review

Ponmalar

Sarangi

Basu

et al. 2021

Front. Mol. Biosci.

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Protein–phospholipid interplay revealed with crystals of a calcium pump

Norimatsu

Hasegawa

Shimizu

et al. 2017

Nature

129

142

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The lipid bilayer has so far eluded visualization by conventional crystallographic methods, severely limiting our understanding of phospholipid- and protein-phospholipid interactions. Here we describe electron density maps for crystals of Ca-ATPase in four different states obtained by X-ray solvent contrast modulation. These maps resolve the entire first layer of phospholipids surrounding the transmembrane helices, although less than half of them are hydrogen-bonded to protein residues. Phospholipids follow the movements of associated residues, causing local distortions and changes in thickness of the bilayer. Unexpectedly, the entire protein tilts during the reaction cycle, governed primarily by a belt of Trp residues, to minimize energy costs accompanying the large perpendicular movements of the transmembrane helices. A class of Arg residues extend their side chains through the cytoplasm to exploit phospholipids as anchors for conformational switching. Thus, phospholipid-Arg/Lys and phospholipid-Trp interactions have distinct functional roles in the dynamics of ion pumps and, presumably, membrane proteins in general.

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Neutrons to Study the Structure and Dynamics of Membrane Proteins

Cited by 2 publications

References 48 publications

Pore Forming Protein Induced Biomembrane Reorganization and Dynamics: A Focused Review

Pore Forming Protein Induced Biomembrane Reorganization and Dynamics: A Focused Review

Protein–phospholipid interplay revealed with crystals of a calcium pump

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