The Amyloid Structure of Mouse RIPK3 (Receptor Interacting Protein Kinase 3) in Cell Necroptosis

ABSTRACTRIPK3 amyloid complex plays crucial roles in execution of TNF-induced necroptosis and in response to immune defense in both human and mouse. We have structurally characterized the mouse RIPK3 homogeneous self-assembly using solid-state NMR, illustrating a well-ordered N-shaped amyloid core structure featured with 3 parallel in-register β-sheets. The structure is different from previously published human RIPK1/RIPK3 hetero-amyloid complex. Functional studies indicate both RIPK1-RIPK3 binding and RIPK3 amyloid formation are essential but not sufficient for RIPK3-mediated necroptosis. The structural integrity of RIPK3 fibril with three β-strands is necessary for the signaling. Molecular dynamics simulation of the mouse RIPK1/RIPK3 model indicates less stable for the hetero-amyloid to adopt RIPK3 fibril conformation, suggesting a structural transformation of RIPK3 from RIPK1-RIPK3 binding to RIPK3 amyloid formation. This structural transformation is revealed for the first time, providing a missing link connecting RIPK1-RIPK3 binding to RIPK3 homo-oligomer formation in the signal transduction.

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The amyloid structure of mouse RIPK3 (receptor interacting protein kinase 3) in cell necroptosis

Nature Communications ◽

10.1038/s41467-021-21881-2 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Xia-lian Wu ◽

Hong Hu ◽

Xing-qi Dong ◽

Jing Zhang ◽

Jian Wang ◽

...

Keyword(s):

Structural Transformation ◽

Self Assembly ◽

Structural Integrity ◽

Complex Structure ◽

Immune Defense ◽

Amyloid Formation ◽

Interacting Protein ◽

Functional Studies ◽

Dynamics Simulations ◽

Human And Mouse

AbstractRIPK3 amyloid complex plays crucial roles during TNF-induced necroptosis and in response to immune defense in both human and mouse. Here, we have structurally characterized mouse RIPK3 homogeneous self-assembly using solid-state NMR, revealing a well-ordered N-shaped amyloid core structure featured with 3 parallel in-register β-sheets. This structure differs from previously published human RIPK1/RIPK3 hetero-amyloid complex structure, which adopted a serpentine fold. Functional studies indicate both RIPK1-RIPK3 binding and RIPK3 amyloid formation are essential but not sufficient for TNF-induced necroptosis. The structural integrity of RIPK3 fibril with three β-strands is necessary for signaling. Molecular dynamics simulations with a mouse RIPK1/RIPK3 model indicate that the hetero-amyloid is less stable when adopting the RIPK3 fibril conformation, suggesting a structural transformation of RIPK3 from RIPK1-RIPK3 binding to RIPK3 amyloid formation. This structural transformation would provide the missing link connecting RIPK1-RIPK3 binding to RIPK3 homo-oligomer formation in the signal transduction.

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A dissipative particle dynamics simulation study on phase diagrams for the self-assembly of amphiphilic hyperbranched multiarm copolymers in various solvents

Soft Matter ◽

10.1039/c7sm01170a ◽

2017 ◽

Vol 13 (36) ◽

pp. 6178-6188 ◽

Cited By ~ 20

Author(s):

Haina Tan ◽

Chunyang Yu ◽

Zhongyuan Lu ◽

Yongfeng Zhou ◽

Deyue Yan

Keyword(s):

Phase Diagrams ◽

Simulation Study ◽

Self Assembly ◽

Dissipative Particle Dynamics ◽

Particle Dynamics ◽

The Self ◽

Dynamics Simulation ◽

Dynamics Simulations ◽

First Time ◽

Dissipative Particle Dynamics Simulation

This work discloses for the first time the self-assembly phase diagrams of amphiphilic hyperbranched multiarm copolymers in various solvents by dissipative particle dynamics simulations.

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miR-29a-3p directly targets Smad nuclear interacting protein 1 and inhibits the migration and proliferation of cervical cancer HeLa cells

PeerJ ◽

10.7717/peerj.10148 ◽

2020 ◽

Vol 8 ◽

pp. e10148

Author(s):

Ying Chen ◽

Weiji Zhang ◽

Lijun Yan ◽

Peng Zheng ◽

Jin Li

Keyword(s):

Cervical Cancer ◽

Cancer Progression ◽

Hela Cells ◽

Luciferase Reporter ◽

Interacting Protein ◽

Over Expression ◽

Functional Studies ◽

Novel Mirna ◽

Mrna And Protein Expression ◽

First Time

Smad nuclear interacting protein 1 (SNIP1) is a nuclear protein and involved in essential biological processes. MicroRNAs are effective regulators of tumorigenesis and cancer progression via targeting multiple genes. In present study, we aimed to investigate the function of SNIP1 and identify novel miRNA-SNIP1 axis in the development of cervical cancer. The results showed for the first time that silencing of the SNIP1 gene inhibited the migration and proliferation in HeLa cells significantly. Bioinformatics analysis and dual luciferase reporter assay demonstrated that miR-29a-3p could target 3′ UTR of SNIP1 directly. The mRNA and protein expression levels of SNIP1 were negative regulated by miR-29a-3p according to the RT-qPCR and Western blot analysis, respectively. Furthermore, functional studies showed that over-expression of miR-29a-3p restrained HeLa cells migration and proliferation, and the mRNA expression of SNIP1 downstream genes (HSP27, c-Myc, and cyclin D1) were down-regulated by miR-29a-3p. Together, we concluded that miR-29a-3p suppressed the migration and proliferation in HeLa cells by directly targeting SNIP1. The newly identified miR-29a-3p/SNIP1 axis could provide new insight into the development of cervical cancer.

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Single Amino Acid Based Self-Assemblies of Cysteine and Methionine

10.26434/chemrxiv.5972173.v1 ◽

2018 ◽

Author(s):

Nidhi Gour ◽

Bharti Koshti ◽

Chandra Kanth P. ◽

Dhruvi Shah ◽

Vivek Shinh Kshatriya ◽

...

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Self Assembly ◽

Aromatic Amino Acids ◽

Neutral Condition ◽

Single Amino Acid ◽

Binding Assays ◽

Human Neuroblastoma ◽

Cytotoxicity Assays ◽

First Time

We report for the very first time self-assembly of Cysteine and Methionine to discrenible strucutres under neutral condition. To get insights into the structure formation, thioflavin T and Congo red binding assays were done which revealed that aggregates may not have amyloid like characteristics. The nature of interactions which lead to such self-assemblies was purported by coincubating assemblies in urea and mercaptoethanol. Further interaction of aggregates with short amyloidogenic dipeptide diphenylalanine (FF) was assessed. While cysteine aggregates completely disrupted FF fibres, methionine albeit triggered fibrillation. The cytotoxicity assays of cysteine and methionine structures were performed on Human Neuroblastoma IMR-32 cells which suggested that aggregates are not cytotoxic in nature and thus, may not have amyloid like etiology. The results presented in the manuscript are striking, since to the best of our knowledge,this is the first report which demonstrates that even non-aromatic amino acids (cysteine and methionine) can undergo spontaneous self-assembly to form ordered aggregates.

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Probing the Dynamic Self-Assembly Behaviour of Photoswitchable Wormlike Micelles in Real Time

10.26434/chemrxiv.7098695 ◽

2018 ◽

Author(s):

Elaine A. Kelly ◽

Judith E. Houston ◽

Rachel Evans

Keyword(s):

Real Time ◽

Absorption Spectroscopy ◽

Self Assembly ◽

Uv Light ◽

Wormlike Micelles ◽

Tetraethylene Glycol ◽

Light Illumination ◽

First Time ◽

Dependent Processes

Understanding the dynamic self-assembly behaviour of azobenzene photosurfactants (AzoPS) is crucial to advance their use in controlled release applications such asdrug delivery and micellar catalysis. Currently, their behaviour in the equilibrium cis-and trans-photostationary states is more widely understood than during the photoisomerisation process itself. Here, we investigate the time-dependent self-assembly of the different photoisomers of a model neutral AzoPS, <a>tetraethylene glycol mono(4′,4-octyloxy,octyl-azobenzene) </a>(C8AzoOC8E4) using small-angle neutron scattering (SANS). We show that the incorporation of in-situUV-Vis absorption spectroscopy with SANS allows the scattering profile, and hence micelle shape, to be correlated with the extent of photoisomerisation in real-time. It was observed that C8AzoOC8E4could switch between wormlike micelles (transnative state) and fractal aggregates (under UV light), with changes in the self-assembled structure arising concurrently with changes in the absorption spectrum. Wormlike micelles could be recovered within 60 seconds of blue light illumination. To the best of our knowledge, this is the first time the degree of AzoPS photoisomerisation has been tracked in-situthrough combined UV-Vis absorption spectroscopy-SANS measurements. This technique could be widely used to gain mechanistic and kinetic insights into light-dependent processes that are reliant on self-assembly.

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Multicanonical Molecular Dynamics Simulation Study of the Liquid-Solid and Solid-Solid Transitions in Lennard-Jones Clusters

ASME/JSME 2011 8th Thermal Engineering Joint Conference ◽

10.1115/ajtec2011-44457 ◽

2011 ◽

Author(s):

Toshihiro Kaneko ◽

Kenji Yasuoka ◽

Ayori Mitsutake ◽

Xiao Cheng Zeng

Keyword(s):

Molecular Dynamics ◽

Heat Capacity ◽

Transition Temperature ◽

Peak Position ◽

Temperature Curve ◽

Dynamics Simulation ◽

Lennard Jones ◽

Dynamics Simulations ◽

First Time ◽

Good Agreement

Multicanonical molecular dynamics simulations are applied, for the first time, to study the liquid-solid and solid-solid transitions in Lennard-Jones (LJ) clusters. The transition temperatures are estimated based on the peak position in the heat capacity versus temperature curve. For LJ31, LJ58 and LJ98, our results on the solid-solid transition temperature are in good agreement with previous ones. For LJ309, the predicted liquid-solid transition temperature is also in agreement with previous result.

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Interactions between an Associative Amphiphilic Block Polyelectrolyte and Surfactants in Water: Effect of Charge Type on Solution Properties and Aggregation

Polymers ◽

10.3390/polym13111729 ◽

2021 ◽

Vol 13 (11) ◽

pp. 1729

Author(s):

Patrizio Raffa

Keyword(s):

Surface Tension ◽

Self Assembly ◽

Interaction Model ◽

Industrial Applications ◽

Molecular Organization ◽

Different Types ◽

Solution Rheology ◽

Interesting Class ◽

First Time

The study of interactions between polyelectrolytes (PE) and surfactants is of great interest for both fundamental and applied research. These mixtures can represent, for example, models of self-assembly and molecular organization in biological systems, but they are also relevant in industrial applications. Amphiphilic block polyelectrolytes represent an interesting class of PE, but their interactions with surfactants have not been extensively explored so far, most studies being restricted to non-associating PE. In this work, interactions between an anionic amphiphilic triblock polyelectrolyte and different types of surfactants bearing respectively negative, positive and no charge, are investigated via surface tension and solution rheology measurements for the first time. It is evidenced that the surfactants have different effects on viscosity and surface tension, depending on their charge type. Micellization of the surfactant is affected by the presence of the polymer in all cases; shear viscosity of polymer solutions decreases in presence of the same charge or nonionic surfactants, while the opposite charge surfactant causes precipitation. This study highlights the importance of the charge type, and the role of the associating hydrophobic block in the PE structure, on the solution behavior of the mixtures. Moreover, a possible interaction model is proposed, based on the obtained data.

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Modeling and Molecular Dynamics of the 3D Structure of the HPV16 E7 Protein and Its Variants

International Journal of Molecular Sciences ◽

10.3390/ijms22031400 ◽

2021 ◽

Vol 22 (3) ◽

pp. 1400

Author(s):

Ciresthel Bello-Rios ◽

Sarita Montaño ◽

Olga Lilia Garibay-Cerdenares ◽

Lilian Esmeralda Araujo-Arcos ◽

Marco Antonio Leyva-Vázquez ◽

...

Keyword(s):

Molecular Dynamics ◽

3D Structure ◽

Epidemiological Studies ◽

Dynamics Simulation ◽

Structural Refinement ◽

Oncogenic Potential ◽

Structural Differences ◽

Reference Protein ◽

E6 And E7 ◽

First Time

The oncogenic potential of high-risk human papillomavirus (HPV) is predicated on the production of the E6 and E7 oncoproteins, which are responsible for disrupting the control of the cell cycle. Epidemiological studies have proposed that the presence of the N29S and H51N variants of the HPV16 E7 protein is significantly associated with cervical cancer. It has been suggested that changes in the amino acid sequence of E7 variants may affect the oncoprotein 3D structure; however, this remains uncertain. An analysis of the structural differences of the HPV16 E7 protein and its variants (N29S and H51N) was performed through homology modeling and structural refinement by molecular dynamics simulation. We propose, for the first time, a 3D structure of the E7 reference protein and two of Its variants (N29S and H51N), and conclude that the mutations induced by the variants in N29S and H51N have a significant influence on the 3D structure of the E7 protein of HPV16, which could be related to the oncogenic capacity of this protein.

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Taming nitroformate through encapsulation with nitrogen-rich hydrogen-bonded organic frameworks

Nature Communications ◽

10.1038/s41467-021-22475-8 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Jichuan Zhang ◽

Yongan Feng ◽

Richard J. Staples ◽

Jiaheng Zhang ◽

Jean’ne M. Shreeve

Keyword(s):

Thermal Stability ◽

Hydrogen Bonds ◽

Self Assembly ◽

Energetic Materials ◽

Decomposition Temperature ◽

High Oxygen Content ◽

The Poor ◽

Simple Preparation ◽

First Time ◽

Hydrogen Bonded

AbstractOwing to its simple preparation and high oxygen content, nitroformate [−C(NO2)3, NF] is an extremely attractive oxidant component for propellants and explosives. However, the poor thermostability of NF-based derivatives has been an unconquerable barrier for more than 150 years, thus hindering its application. In this study, the first example of a nitrogen-rich hydrogen-bonded organic framework (HOF-NF) is designed and constructed through self-assembly in energetic materials, in which NF anions are trapped in pores of the resulting framework via the dual force of ionic and hydrogen bonds from the strengthened framework. These factors lead to the decomposition temperature of the resulting HOF-NF moiety being 200 °C, which exceeds the challenge of thermal stability over 180 °C for the first time among NF-based compounds. A large number of NF-based compounds with high stabilities and excellent properties can be designed and synthesized on the basis of this work.

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