CryoVIA: An image analysis toolkit for the quantification of membrane structures from cryo-EM micrographs DOI Creative Commons
Philipp Schönnenbeck, Benedikt Junglas, Carsten Sachse

et al.

Structure, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Highlights•A software suite for automated analysis of lipid membranes in electron micrographs•Includes segmentation, shape identification, and membrane properties•Applied to datasets with different lipids protein-induced changes•Features an intuitive GUI batch micrograph analysisSummaryImaging structures associated protein complexes using cryoelectron microscopy (cryo-EM) is a common visualization structure determination technique. The quantitative the structures, however, not routine time consuming particular when large amounts data are involved. Here, we introduce image-processing cryo-vesicle image analyzer (CryoVIA) that parametrizes from cryo-EM images. This toolkit combines identification methods automatically perform large-scale local global properties such as bilayer thickness, size, curvature including classifications. We included analyses exemplary compositions changes through endosomal sorting required transport III (ESCRT-III) remodeling protein. opens new possibilities systematically study structural their modifications images.Graphical abstract

Language: Английский

Mechanical activation opens a lipid-lined pore in OSCA ion channels DOI
Yaoyao Han,

Zijing Zhou,

Ruitao Jin

et al.

Nature, Journal Year: 2024, Volume and Issue: 628(8009), P. 910 - 918

Published: April 3, 2024

Language: Английский

Citations

36

Ion and lipid orchestration of secondary active transport DOI
David Drew,

Olga Boudker

Nature, Journal Year: 2024, Volume and Issue: 626(8001), P. 963 - 974

Published: Feb. 28, 2024

Language: Английский

Citations

27

High-resolution electron cryomicroscopy of V-ATPase in native synaptic vesicles DOI
Claire E. Coupland, Ryan Karimi, Stephanie A. Bueler

et al.

Science, Journal Year: 2024, Volume and Issue: 385(6705), P. 168 - 174

Published: June 20, 2024

Intercellular communication in the nervous system occurs through release of neurotransmitters into synaptic cleft between neurons. In presynaptic neuron, proton pumping vesicular- or vacuolar-type ATPase (V-ATPase) powers neurotransmitter loading vesicles (SVs), with V 1 complex dissociating from membrane region enzyme before exocytosis. We isolated SVs rat brain using SidK, a V-ATPase–binding bacterial effector protein. Single-particle electron cryomicroscopy allowed high-resolution structure determination V-ATPase within native SV membrane. structure, regularly spaced cholesterol molecules decorate enzyme’s rotor and abundant protein synaptophysin binds stoichiometrically. ATP hydrolysis during vesicle results loss membrane, suggesting that is sufficient to induce dissociation enzyme.

Language: Английский

Citations

25

Cell membranes sustain phospholipid imbalance via cholesterol asymmetry DOI
Milka Doktorova, Jessica L. Symons,

Xiaoxuan Zhang

et al.

Cell, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

Citations

5

Transient Receptor Potential Channels in Dental Inflammation and Pain Perception: A Comprehensive Review DOI Creative Commons

Varunya Chantadul,

Nattapon Rotpenpian, Tawepong Arayapisit

et al.

Heliyon, Journal Year: 2025, Volume and Issue: 11(2), P. e41730 - e41730

Published: Jan. 1, 2025

Transient Receptor Potential (TRP) channels are a family of ion that play pivotal roles in various physiological processes, including sensory transduction, temperature regulation, and inflammation. In the context dentistry, recent research has highlighted involvement TRP mediating responses inflammation dental tissues temporo-mandibular joint (TMJ) structure. have emerged as major contributors development inflammatory conditions pain affecting oral cavity related structures, such periodontitis, erosion cause hypersensitivity, pulpitis, TMJ disorders. These notably contribute to health challenges, often leading sharp pain, dull aches, compromised functionality. Pharmacological interventions emerging strategies aimed at modulating channel activity critically evaluated. The therapeutic potential targeting management within practice is focal point view alleviate conclusion, this comprehensive review provides valuable synthesis current knowledge regarding dentistry underscoring promising targets for intervention, then paving way innovative address complexities conditions.

Language: Английский

Citations

2

Cell Membranes Sustain Phospholipid Imbalance Via Cholesterol Asymmetry DOI Creative Commons
Milka Doktorova, Jessica L. Symons,

Xiaoxuan Zhang

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: July 31, 2023

Membranes are molecular interfaces that compartmentalize cells to control the flow of nutrients and information. These functions facilitated by diverse collections lipids, nearly all which distributed asymmetrically between two bilayer leaflets. Most models biomembrane structure function often include implicit assumption these leaflets have similar abundances phospholipids. Here, we show this is generally invalid investigate consequences lipid abundance imbalances in mammalian plasma membranes (PM). Using quantitative lipidomics, discovered cytoplasmic human erythrocyte >50% overabundance phospholipids compared exoplasmic This imbalance enabled an asymmetric interleaflet distribution cholesterol, regulates cellular cholesterol homeostasis. features produce unique functional characteristics, including low PM permeability resting tension leaflet protein localization. largely overlooked aspects membrane asymmetry represent evolution classic paradigms physiology.

Language: Английский

Citations

31

Computational drug development for membrane protein targets DOI
Haijian Li, Xiaolin Sun, Wenqiang Cui

et al.

Nature Biotechnology, Journal Year: 2024, Volume and Issue: 42(2), P. 229 - 242

Published: Feb. 1, 2024

Language: Английский

Citations

17

A conserved fertilization complex bridges sperm and egg in vertebrates DOI Creative Commons
Victoria E. Deneke, Andreas Blaha, Yonggang Lu

et al.

Cell, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 1, 2024

Language: Английский

Citations

16

Structure of the flotillin complex in a native membrane environment DOI Creative Commons
Ziao Fu, Roderick MacKinnon

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(29)

Published: July 10, 2024

In this study, we used cryoelectron microscopy to determine the structures of Flotillin protein complex, part Stomatin, Prohibitin, Flotillin, and HflK/C (SPFH) superfamily, from cell-derived vesicles without detergents. It forms a right-handed helical barrel consisting 22 pairs Flotillin1 Flotillin2 subunits, with diameter 32 nm at its wider end 19 narrower end. Oligomerization is stabilized by C terminus, which two layers linked β-strand, coiled-coil domains that enable strong charge–charge intersubunit interactions. interacts membranes both ends; through SPFH1 wide terminus narrow end, facilitated hydrophobic interactions lipidation. The inward tilting SPFH domain, likely triggered phosphorylation, suggests role in membrane curvature induction, could be connected proposed clathrin-independent endocytosis. structure shared architecture across family proteins will promote further research into Flotillin’s roles cell biology.

Language: Английский

Citations

12

Elucidating the Cell Surfaceome to Accelerate Cancer Drug Development DOI Open Access
Jacob B. Geri,

William Pao

Cancer Discovery, Journal Year: 2024, Volume and Issue: 14(4), P. 639 - 642

Published: April 4, 2024

Summary: Cell surface proteins represent ideal therapeutic targets because of their accessibility to antibodies, T cell–directed therapies, and radiotherapies, but there are only 25 therapeutically relevant cell for which cancer therapies approved in the United States or European Union. This commentary calls intensified research into mapping universe – surfaceome order accelerate drug development.

Language: Английский

Citations

9