Rotation and Self-Assembly Driving NLRP3 Activation DOI
Haochen Xu, Zhonghuai Hou, Rongbin Zhou

et al.

Journal of Chemical Information and Modeling, Journal Year: 2024, Volume and Issue: 64(17), P. 6857 - 6865

Published: Aug. 27, 2024

As a critical sensor protein, NLRP3 detects cellular perturbation caused by diverse exogenous and endogenous stimuli. activation requires domain rotation within the NEK7-bound monomer assembly. However, detailed molecular mechanism for assembly remains elusive, particularly in terms of dynamics energetics. In this work, all-atom (MD) simulations are executed to describe large-amplitude closed-to-open conformational transitions along rotational pathway. From MD trajectories, computed potential mean force (PMF) shows that through monomeric is an uphill process, during which active conformation NLRP3-NEK7 cannot be stabilized. Further binding free-energy calculations two neighboring subunits disc with C10 symmetry reveal protein self-assembly starts approximately at 86.5° position on rotary pathway, becomes downhill process state 90.5°. The stabilized because interactions between subunits, involving mainly FISNA loop 1 one subunit "crocodile-clip" structure formed NBD helix-loop-strand motif (residues 351-373) WHD β-hairpin 501-521) other. Our also demonstrate NEK7 plays important role cage dissociation centrosome, consistent biological experiments. computational results provide kinetic, energetic, structural insights into mechanisms NEK7-driven inactive cages. proposed work significantly different from those previous studies.

Language: Английский

Terahertz wave alleviates comorbidity anxiety in pain by reducing the binding capacity of nanostructured glutamate molecules to GluA2 DOI Creative Commons

Zihua Song,

Yuankun Sun, Pan Liu

et al.

Research, Journal Year: 2024, Volume and Issue: 7

Published: Jan. 1, 2024

Comorbid anxiety in chronic pain is clinically common, with a comorbidity rate of over 50%. The main treatments are based on pharmacological, interventional, and implantable approaches, which have limited efficacy carry risk side effects. Here, we report terahertz (THz, 10 12 Hz) wave stimulation (THS) technique, exerts nonthermal, long-term modulatory effects neuronal activity by reducing the binding between nano-sized glutamate molecules GluA2, leading to relief comorbid anxiety-like behaviors mice. In mice co-occurring induced complete Freund’s adjuvant (CFA) injection, hyperactivity was observed glutamatergic neurons anterior cingulate cortex (ACC Glu ). Using whole-cell recording ACC slices, demonstrated that THS (34 THz) effectively inhibited excitability . Moreover, molecular dynamics simulations showed reduced number hydrogen bonds bound GluA2. Furthermore, target CFA-treatment suppressed and, as result, alleviated behaviors. Consistently, inhibition chemogenetics mimics THS-induced antinociceptive antianxiety behavior. Together, our study provides evidence for an intervention technique modulating viable clinical treatment strategy anxiety.

Language: Английский

Citations

28

Bulbil initiation: a comprehensive review on resources, development, and utilisation, with emphasis on molecular mechanisms, advanced technologies, and future prospects DOI Creative Commons

Fuxing Shu,

Dongdong Wang, Surendra Sarsaiya

et al.

Frontiers in Plant Science, Journal Year: 2024, Volume and Issue: 15

Published: April 8, 2024

Bulbil is an important asexual reproductive structure of bulbil plants. It mainly grows in leaf axils, forks, tubers and the upper near ground ends flower stems They play a significant role reproduction numerous herbaceous plant species by serving as agents propagation, energy reserves, survival mechanisms adverse environmental conditions. Despite extensive research on bulbil-plants regarding their resources, development mechanisms, utilisation, comprehensive review lacking, hindering progress exploiting resources. This paper provides systematic overview research, including bulbil-plant identification stages maturity bulbils, cellular molecular development, factors influencing gene related to multi-bulbil phenomenon its significance, medicinal value breeding application tissue culture technology production. The Temporary Immersion Bioreactor System (TIBS) Terahertz (THz) also discussed, offering blueprint for further resource development. Additionally, additive, seven areas that require attention are proposed: (1) Utilization modern network technologies, such recognition apps or websites, collect identify bulbous resources efficiently extensively; (2) Further cell structures influence bulb development; (3) Investigation regulatory relationship between genes, proteins, metabolites, epigenetics (4) Exploration potential utilization multiple sprouts, medicinal, ecological, horticultural applications; (5) Innovation optimization system bulbils; (6) Comprehensive TIBS large-scale expansion production; (7) To find out common share genetics bulbils flowers.

Language: Английский

Citations

6

Dissociation of Nicotine from Acetylcholine-Binding Protein under Terahertz Waves Radiation DOI
Chen Chen,

Haotian Hao,

Mengqiu Li

et al.

The Journal of Physical Chemistry B, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 27, 2024

The binding of nicotine (NCT) to acetylcholine-binding protein (AChBP) plays an important role in synaptic transmission and neurotransmitter regulation. However, effectively regulating their or dissociation processes remains a challenging problem. In this study, we employed all-atom molecular dynamics (MD) simulations systematically investigate the impact external terahertz (THz) waves on kinetics between AChBP NCT. We first identified key residues (i.e., W143) interactions hydrogen bonding cation-π interaction) AChBP-NCT without THz waves. then investigated charged NCT with at three different frequencies 13.02, 21.44, 42.55 THz). Importantly, predominant vibrational modes 13.02 can drive rotation pentagonal ring This leads disruption bonds W143 reduced likelihood forming interactions, resulting from AChBP. Additionally, further influence electric field intensities found that when intensity exceeds critical value (∼0.60 V/nm), probability ligand gradually rises as increases. general, study contributes better understanding effects protein-ligand which might also shed some light potential applications addiction treatment therapeutic strategies for neurodegenerative diseases.

Language: Английский

Citations

5

Origins of the Superiority of Oscillating Electric Fields for Disrupting Senile Plaques: Insights from the 7-Residue Fragment and the Full-length Aβ-42 Peptide DOI Creative Commons
Surajit Kalita, David Danovich, Sason Shaik

et al.

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 8, 2025

Our recent molecular dynamics simulations of decomposing Alzheimer's disease plaques, under oscillating- and static external electric fields (Os-EEFs St-EEFs), revealed the superiority Os-EEF for plaques consisting 7-residue peptide segment. This conclusion is now reinforced by studying dimers short peptides trimers full-length Aβ-42 peptide. Thus, dispersed obtained following St-EEF applications reformed once subsided. In contrast, originating from application remained long time scales. The present study provides insights into these results modeling decomposition modes that transpire both field types. Additionally, this frequency effects on processes within THz–MHz regions. simulation shows in lower range (≤GHz) decomposes plaque a scale ∼50 ns, whereas higher Os-EEFs (≥THz) are less effective. As such, with moderate-to-low frequencies lead to an "explosion," whereby fly distantly apart inhibit reformation. By St-EEFs form parallel pairs, which stabilized EEF due large dipole moment ensemble. sluggish reversible processes. We further conclude impact maximal pulses, prevents propensity arrange pairs. over maintained irrespective peptides' length. A model formulated predicts dependence EEF.

Language: Английский

Citations

0

Membrane-assisted Aβ40 aggregation pathways DOI Creative Commons

Fidha Nazreen Kunnath Muhammedkutty,

Huan‐Xiang Zhou

Cell Reports Physical Science, Journal Year: 2025, Volume and Issue: 6(2), P. 102436 - 102436

Published: Feb. 1, 2025

Highlights•Membrane association of Aβ40 initiates multiple pathways, leading to polymorphism•Membranes facilely stabilize small oligomeric seeds•Key residues facilitate an ordered release seeds from membranes•Polymorphic fibrils may share structural motifs and be related by domain swapSummaryAlzheimer's disease (AD) is caused the assembly amyloid-beta (Aβ) peptides into oligomers fibrils. Endogenous Aβ aggregation assisted cell membranes, which can accelerate nucleation step enormously, but knowledge membrane-assisted still very limited. Here, we used extensive molecular dynamics (MD) simulations structurally energetically characterize key intermediates along pathways Aβ40. Reinforcing experimental observations, reveal unique roles GM1 ganglioside cholesterol in stabilizing membrane-embedded β sheets Y10 K28 a seed solution. The same leads either open-shaped or R-shaped fibril, with significant stabilization provided inter- intra-subunit interfaces between straight sheet (residues Q15–D23) bent A30–V36). This work presents comprehensive picture Aβ40, broad implications for developing AD therapies rationalizing disease-specific polymorphisms amyloidogenic proteins.Graphical abstract

Language: Английский

Citations

0

Terahertz waves promote Ca2+ transport in the Cav2.1 channel DOI
Yuankun Sun, Yangmei Li, Yaxiong Yang

et al.

Spectrochimica Acta Part A Molecular and Biomolecular Spectroscopy, Journal Year: 2025, Volume and Issue: unknown, P. 126039 - 126039

Published: March 1, 2025

Language: Английский

Citations

0

Delving into the crucial role of the initial structure in the dynamic and self-assembly of amyloid beta DOI

Maryam Ghorbaninia,

Shirin Doroudgar,

Mohamad Reza Ganjalikhany

et al.

Biochemical and Biophysical Research Communications, Journal Year: 2025, Volume and Issue: 758, P. 151652 - 151652

Published: March 17, 2025

Language: Английский

Citations

0

Terahertz waves facilitate capsaicin expulsion from TRPV1 DOI
Zhi Zhu,

Juan-Xia Zhu,

Shiyu Gu

et al.

The Journal of Chemical Physics, Journal Year: 2025, Volume and Issue: 162(18)

Published: May 8, 2025

Transient receptor potential vanilloid 1 (TRPV1) is a critical non-selective cation channel involved in various biological and physiological processes, making it promising drug target for treating multiple diseases. Capsaicin, TRPV1 agonist, widely used to relieve pain by desensitizing the with persistent stimulation. However, initially intolerable burning sensation due activation necessitates use of antagonists deactivate mitigate discomfort, which yet causes thermoregulation disorders. In this study, molecular dynamics simulations reveal that frequency-specific terahertz (THz) waves can promote capsaicin unbinding from TRPV1, suggesting spatiotemporally controlled approach deactivation. The THz wave resonates hydroxyl group head, increasing its rotational kinetic energy promoting rotation. This disrupts key hydrogen bond between residue E570, significantly reducing capsaicin’s affinity TRPV1. Our findings suggest could mimic more flexible way, offering temporal control over recruitment expulsion (i.e., activation, desensitization, deactivation) comfortable relief. addition, work enlightens THz-based, pill-free strategy induced inflammatory ligands activated

Language: Английский

Citations

0

Effect of terahertz waves on the aggregation behavior of neurotransmitters DOI
Mengqiu Li, Chen Chen, Yu‐qiang Ma

et al.

Physical Chemistry Chemical Physics, Journal Year: 2024, Volume and Issue: 26(18), P. 13751 - 13761

Published: Jan. 1, 2024

By using all-atom molecular dynamics simulation, we reveal a nuanced relationship between THz frequencies and neurotransmitter aggregation.

Language: Английский

Citations

3

Influence of Terahertz Waves on the Binding of Choline to Choline Acetyltransferase: Insights from Molecular Dynamics Simulations DOI

Hui Ning,

Kaicheng Wang, Qin Zhang

et al.

Physical Chemistry Chemical Physics, Journal Year: 2024, Volume and Issue: 26(34), P. 22413 - 22422

Published: Jan. 1, 2024

Using molecular dynamics, we studied the impact of THz waves on choline binding to acetyltransferase and found that specific frequencies can influence this binding, potentially affecting acetylcholine synthesis.

Language: Английский

Citations

2