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1.
Proc Natl Acad Sci U S A ; 118(8)2021 02 23.
Artículo en Inglés | MEDLINE | ID: mdl-33602811

RESUMEN

Locomotion of an organism interacting with an environment is the consequence of a symmetry-breaking action in space-time. Here we show a minimal instantiation of this principle using a thin circular sheet, actuated symmetrically by a pneumatic source, using pressure to change shape nonlinearly via a spontaneous buckling instability. This leads to a polarized, bilaterally symmetric cone that can walk on land and swim in water. In either mode of locomotion, the emergence of shape asymmetry in the sheet leads to an asymmetric interaction with the environment that generates movement--via anisotropic friction on land, and via directed inertial forces in water. Scaling laws for the speed of the sheet of the actuator as a function of its size, shape, and the frequency of actuation are consistent with our observations. The presence of easily controllable reversible modes of buckling deformation further allows for a change in the direction of locomotion in open arenas and the ability to squeeze through confined environments--both of which we demonstrate using simple experiments. Our simple approach of harnessing elastic instabilities in soft structures to drive locomotion enables the design of novel shape-changing robots and other bioinspired machines at multiple scales.

2.
Mol Pharm ; 20(2): 1247-1255, 2023 02 06.
Artículo en Inglés | MEDLINE | ID: mdl-36563318

RESUMEN

Endothelin receptor A (ETA), a class A G protein-coupled receptor (GPCR), is a promising tumor-associated antigen due to its close association with the progression and metastasis of many types of cancer, such as colorectal, breast, lung, ovarian, and prostate cancer. However, only small-molecule drugs have been developed as ETA antagonists with anticancer effects. In a previous study, we identified an antibody (AG8) with highly selective binding to human ETA through screening of a human naïve immune antibody library. Although both in vitro and in vivo experiments indicated that the identified AG8 had anticancer effects, there is a need for improvement in biochemical and physicochemical properties such as the ETA binding affinity, thermostability, and productivity. In this study, we engineered the framework regions of AG8 and isolated an anti-ETA antibody (MJF1) exhibiting significantly improved thermostability and ETA binding affinity. Subsequently, our previously isolated PFc29, an Fc variant with an enhanced pH-dependent human FcRn binding profile, was introduced to MJF1, and the resulting Fc-engineered anti-ETA antibody (MJF1-PFc29) inhibited the proliferation of tumor cells comparably to MJF1 and showed a 4.2-fold increased serum half-life in human FcRn transgenic mice. Moreover, MJF1-PFc29 elicited higher tumor growth inhibition in colorectal cancer xenograft mice compared to MJF1. Our results demonstrate that the engineered human anti-ETA antibody MJF1-PFc29 has great therapeutic potential and high antitumor potency against various types of cancers including colorectal cancer.


Asunto(s)
Neoplasias Colorrectales , Ingeniería de Proteínas , Masculino , Humanos , Ratones , Animales , Receptores Fc/metabolismo , Ratones Transgénicos , Receptor de Endotelina A , Neoplasias Colorrectales/tratamiento farmacológico
3.
Fish Shellfish Immunol ; 138: 108807, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37169112

RESUMEN

The COVID-19 pandemic has significantly impacted human health for three years. To mitigate the spread of SARS-CoV-2, the development of neutralizing antibodies has been accelerated, including the exploration of alternative antibody formats such as single-domain antibodies. In this study, we identified variable new antigen receptors (VNARs) specific for the receptor binding domain (RBD) of SARS-CoV-2 by immunizing a banded houndshark (Triakis scyllium) with recombinant wild-type RBD. Notably, the CoV2NAR-1 clone showed high binding affinities in the nanomolar range to various RBDs and demonstrated neutralizing activity against SARS-CoV-2 pseudoviruses. These results highlight the potential of the banded houndshark as an animal model for the development of VNAR-based therapeutics or diagnostics against future pandemics.


Asunto(s)
COVID-19 , Anticuerpos de Dominio Único , Humanos , Animales , SARS-CoV-2/metabolismo , Anticuerpos Antivirales , Pandemias , Anticuerpos Neutralizantes
4.
Mar Drugs ; 21(11)2023 Nov 02.
Artículo en Inglés | MEDLINE | ID: mdl-37999400

RESUMEN

Microalgae have gained attention as a promising source of chlorophylls and carotenoids in various industries. However, scaling up of conventional bubble columns presents challenges related to cell sedimentation and the presence of non-photosynthetic cells due to non-circulating zones and decreased light accessibility, respectively. Therefore, this study aimed to evaluate the newly developed continuously circulated bioreactor ROSEMAX at both laboratory and pilot scales, compared to a conventional bubble column. There was no significant difference in the biomass production and photosynthetic pigment content of Tetraselmis sp. cultivated at the laboratory scale (p > 0.05). However, at the pilot scale, the biomass cultured in ROSEMAX showed significantly high biomass (1.69 ± 0.11 g/L, dry weight, DW), chlorophyll-a (14.60 ± 0.76 mg/g, DW), and total carotene (5.64 ± 0.81 mg/g, DW) concentrations compared to the conventional bubble column (1.17 ± 0.11 g/L, DW, 10.67 ± 0.72 mg/g, DW, 3.21 ± 0.56 mg/g, DW, respectively) (p ≤ 0.05). Flow cytometric analyses confirmed that the proportion of Tetraselmis sp. live cells in the culture medium of ROSEMAX was 32.90% higher than that in the conventional bubble column, with a photosynthetic efficiency 1.14 times higher. These results support suggestions to use ROSEMAX as a bioreactor for industrial-scale applications.


Asunto(s)
Microalgas , Fotosíntesis , Reactores Biológicos , Carotenoides/análisis , Clorofila A , Medios de Cultivo , Biomasa
5.
Nano Lett ; 22(14): 5742-5750, 2022 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-35666985

RESUMEN

This paper reports an approach to repurpose low-cost, bulk multilayer MoS2 for development of ultraefficient hydrogen evolution reaction (HER) catalysts over large areas (>cm2). We create working electrodes for use in HER by dry transfer of MoS2 nano- and microflakes to gold thin films deposited on prestrained thermoplastic substrates. By relieving the prestrain at a macroscopic scale, a tunable level of tensile strain is developed in the MoS2 and consequently results in a local phase transition as a result of spontaneously formed surface wrinkles. Using electrochemical impedance spectroscopy, we verified that electrochemical activation of the strained MoS2 lowered the charge transfer resistance within the materials system, achieving HER activity comparable to platinum (Pt). Raman and X-ray photoelectron spectroscopy show that desulfurization in the multilayer MoS2 was promoted by the phase transition; the combined effect of desulfurization and the lower charge resistance induced superior HER performance.

6.
Small ; 18(48): e2205057, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36269881

RESUMEN

Flat metasurfaces with subwavelength meta-atoms can be designed to manipulate the electromagnetic parameters of incident light and enable unusual light-matter interactions. Although hydrogel-based metasurfaces have the potential to control optical properties dynamically in response to environmental conditions, the pattern resolution of these surfaces has been limited to microscale features or larger, limiting capabilities at the nanoscale, and precluding effective use in metamaterials. This paper reports a general approach to developing tunable plasmonic metasurfaces with hydrogel meta-atoms at the subwavelength scale. Periodic arrays of hydrogel nanodots with continuously tunable diameters are fabricated on silver substrates, resulting in humidity-responsive surface plasmon polaritons (SPPs) at the nanostructure-metal interfaces. The peaks of the SPPs are controlled reversibly by absorbing or releasing water within the hydrogel matrix, the matrix-generated plasmonic color rendering in the visible spectrum. This work demonstrates that metasurfaces designed with these spatially patterned nanodots of varying sizes benefit applications in anti-counterfeiting and generate multicolored displays with single-nanodot resolution. Furthermore, this work shows system versatility exhibited by broadband beam-steering on a phase modulator consisting of hydrogel supercell units in which the size variations of constituent hydrogel nanostructures engineer the wavefront of reflected light from the metasurface.


Asunto(s)
Hidrogeles , Nanoestructuras , Plata , Humedad , Agua
7.
Nano Lett ; 21(12): 5430-5437, 2021 Jun 23.
Artículo en Inglés | MEDLINE | ID: mdl-33847117

RESUMEN

The formation of ordered magnetic domains in thin films is important for the magnetic microdevices in spin-electronics, magneto-optics, and magnetic microelectromechanical systems. Although inducing anisotropic stress in magnetostrictive materials can achieve the domain assembly, controlling magnetic anisotropy over microscale areas is challenging. In this work, we realized the microscopic patterning of magnetic domains by engineering stress distribution. Deposition of ferromagnetic thin films on nanotrenched polymeric layers induced tensile stress at the interfaces, giving rise to the directional magnetoelastic coupling to form ordered domains spontaneously. By changing the periodicity and shape of nanotrenches, we spatially tuned the geometric configuration of domains by design. Theoretical analysis and micromagnetic characterization confirmed that the local stress distribution by the topographic confinement dominates the forming mechanism of the directed magnetization.

8.
Mar Drugs ; 19(6)2021 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-34071505

RESUMEN

There is increasing demand for essential fatty acids (EFAs) from non-fish sources such as microalgae, which are considered a renewable and sustainable biomass. The open raceway system (ORS) is an affordable system for microalgae biomass cultivation for industrial applications. However, seasonal variations in weather can affect biomass productivity and the quality of microalgal biomass. The aim of this study was to determine the feasibility of year-round Tetraselmis sp. cultivation in a semi-ORS in Korea for biomass and bioactive lipid production. To maximize biomass productivity of Tetraselmis sp., f medium was selected because it resulted in a significantly higher biomass productivity (1.64 ± 0.03 g/L) and lower omega-6/omega-3 ratio (0.52/1) under laboratory conditions than f/2 medium (0.70/1). Then, we used climatic data-based building information modeling technology to construct a pilot plant of six semi-ORSs for controlling culture conditions, each with a culture volume of 40,000 L. Over 1 year, there were no significant variations in monthly biomass productivity, fatty acid composition, or the omega-6/omega-3 ratio; however, the lipid content correlated significantly with photosynthetic photon flux density. During year-round cultivation from November 2014 to October 2017, areal productivity was gradually increased by increasing medium salinity and injecting CO2 gas into the culture medium. Productivity peaked at 44.01 g/m2/d in October 2017. Throughout the trials, there were no significant differences in average lipid content, which was 14.88 ± 1.26%, 14.73 ± 2.44%, 12.81 ± 2.82%, and 13.63 ± 3.42% in 2014, 2015, 2016, and 2017, respectively. Our results demonstrated that high biomass productivity and constant lipid content can be sustainably maintained under Korean climate conditions.


Asunto(s)
Chlorophyta/metabolismo , Lípidos/biosíntesis , Microalgas/metabolismo , Agricultura/métodos , Biomasa , Medios de Cultivo , Microbiología Industrial/métodos , Proyectos Piloto , República de Corea
9.
Appl Opt ; 59(28): 8918-8924, 2020 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-33104578

RESUMEN

An experimental method is developed for robust frequency stabilization using a high-finesse cavity when the laser exhibits large intermittent frequency jumps. This is accomplished by applying an additional slow feedback signal from Doppler-free fluorescence spectroscopy in an atomic beam with increased frequency locking range. As a result, a stable and narrow-linewidth 556 nm laser maintains the frequency lock status for more than a week and contributes to more accurate evaluation of the Yb optical lattice clock. In addition, the reference optical cavity is supported at vibration-insensitive points without any vibration isolation table, making the laser setup more simple and compact.

10.
Proc Natl Acad Sci U S A ; 114(33): 8734-8739, 2017 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-28760975

RESUMEN

Nanostructured surfaces with quasi-random geometries can manipulate light over broadband wavelengths and wide ranges of angles. Optimization and realization of stochastic patterns have typically relied on serial, direct-write fabrication methods combined with real-space design. However, this approach is not suitable for customizable features or scalable nanomanufacturing. Moreover, trial-and-error processing cannot guarantee fabrication feasibility because processing-structure relations are not included in conventional designs. Here, we report wrinkle lithography integrated with concurrent design to produce quasi-random nanostructures in amorphous silicon at wafer scales that achieved over 160% light absorption enhancement from 800 to 1,200 nm. The quasi-periodicity of patterns, materials filling ratio, and feature depths could be independently controlled. We statistically represented the quasi-random patterns by Fourier spectral density functions (SDFs) that could bridge the processing-structure and structure-performance relations. Iterative search of the optimal structure via the SDF representation enabled concurrent design of nanostructures and processing.

11.
Nano Lett ; 19(8): 5640-5646, 2019 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-31268720

RESUMEN

This paper reports a scalable approach to achieve spatially selective graphene functionalization using multiscale wrinkles. Graphene wrinkles were formed by relieving the strain in thermoplastic polystyrene substrates conformally coated with fluoropolymer and graphene skin layers. Chemical reactivity of a fluorination process could be tuned by changing the local curvature of the graphene nanostructures. Patterned areas of graphene nanowrinkles and crumples followed by a single-process plasma reaction resulted in substrates with regions having different fluorination levels. Notably, conductivity of the functionalized graphene nanostructures could be locally tuned as a function of feature size without affecting the mechanical properties.

12.
Korean J Parasitol ; 58(3): 249-255, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32615738

RESUMEN

Toxoplasma gondii, a ubiquitous, intracellular parasite of the phylum Apicomplexa, infects an estimated one-third of the human population as well as a broad range of warm-blooded animals. We have observed that some tyrosine kinase inhibitors suppressed the growth of T. gondii within host ARPE-10 cells. Among them, afatinib, human epithermal growth factor receptor 2 and 4 (HER2/4) inhibitor, may be used as a therapeutic agent for inhibiting parasite growth with minimal adverse effects on host. In this report, we conducted a proteomic analysis to observe changes in host proteins that were altered via infection with T. gondii and the treatment of HER2/4 inhibitors. Secreting proteins were subjected to a procedure of micor basic reverse phase liquid chromatography, nano-liquid chromatography-mass spectrometry, and ingenuity pathway analysis serially. As a result, the expression level of heterogeneous nuclear ribonucleoprotein K, semaphorin 7A, a GPI membrane anchor, serine/threonine-protein phosphatase 2A, and calpain small subunit 1 proteins were significantly changed, and which were confirmed further by western blot analysis. Changes in various proteins, including these 4 proteins, can be used as a basis for explaining the effects of T. gondii infections and HER2/4 inhibitors.


Asunto(s)
Afatinib/farmacología , Afatinib/uso terapéutico , Interacciones Huésped-Parásitos , Proteínas/metabolismo , Receptor ErbB-2/antagonistas & inhibidores , Toxoplasma/crecimiento & desarrollo , Toxoplasmosis/tratamiento farmacológico , Toxoplasmosis/metabolismo , Antígenos CD/metabolismo , Western Blotting , Línea Celular , Proteínas Ligadas a GPI/metabolismo , Ribonucleoproteínas Nucleares Heterogéneas/metabolismo , Humanos , Proteína Fosfatasa 2/metabolismo , Proteómica/métodos , Semaforinas/metabolismo
13.
J Enzyme Inhib Med Chem ; 34(1): 1481-1488, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31423846

RESUMEN

Indoleamine 2,3-dioxygenase 1 (IDO1), a tryptophan catabolising enzyme, is known as a tumour cell survival factor that causes immune escape in several types of cancer. Flavonoids of Sophora flavescens have a variety of biological benefits for humans; however, cancer immunotherapy effect has not been fully investigated. The flavonoids (1-6) isolated from S. flavescens showed IDO1 inhibitory activities (IC50 4.3-31.4 µM). The representative flavonoids (4-6) of S. flavescens were determined to be non-competitive inhibitors of IDO1 by kinetic analyses. Their binding affinity to IDO1 was confirmed using thermal stability and surface plasmon resonance (SPR) assays. The molecular docking analysis and mutagenesis assay revealed the structural details of the interactions between the flavonoids (1-6) and IDO1. These results suggest that the flavonoids (1-6) of S. flavescens, especially kushenol E (6), as IDO1 inhibitors might be useful in the development of immunotherapeutic agents against cancers.


Asunto(s)
Antineoplásicos/farmacología , Inhibidores Enzimáticos/farmacología , Flavonoides/farmacología , Indolamina-Pirrol 2,3,-Dioxigenasa/antagonistas & inhibidores , Sophora/química , Antineoplásicos/química , Antineoplásicos/aislamiento & purificación , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/aislamiento & purificación , Flavonoides/química , Flavonoides/aislamiento & purificación , Células HeLa , Humanos , Indolamina-Pirrol 2,3,-Dioxigenasa/genética , Indolamina-Pirrol 2,3,-Dioxigenasa/metabolismo , Modelos Moleculares , Estructura Molecular , Mutagénesis Sitio-Dirigida , Relación Estructura-Actividad , Células Tumorales Cultivadas
14.
Proc Natl Acad Sci U S A ; 113(50): 14201-14206, 2016 12 13.
Artículo en Inglés | MEDLINE | ID: mdl-27911819

RESUMEN

Plasmonic nanostructures with enhanced localized optical fields as well as narrow linewidths have driven advances in numerous applications. However, the active engineering of ultranarrow resonances across the visible regime-and within a single system-has not yet been demonstrated. This paper describes how aluminum nanoparticle arrays embedded in an elastomeric slab may exhibit high-quality resonances with linewidths as narrow as 3 nm at wavelengths not accessible by conventional plasmonic materials. We exploited stretching to improve and tune simultaneously the optical response of as-fabricated nanoparticle arrays by shifting the diffraction mode relative to single-particle dipolar or quadrupolar resonances. This dynamic modulation of particle-particle spacing enabled either dipolar or quadrupolar lattice modes to be selectively accessed and individually optimized. Programmable plasmon modes offer a robust way to achieve real-time tunable materials for plasmon-enhanced molecular sensing and plasmonic nanolasers and opens new possibilities for integrating with flexible electronics.

15.
Nano Lett ; 18(7): 4549-4555, 2018 07 11.
Artículo en Inglés | MEDLINE | ID: mdl-29912567

RESUMEN

This paper reports a robust and stretchable nanolaser platform that can preserve its high mode quality by exploiting hybrid quadrupole plasmons as an optical feedback mechanism. Increasing the size of metal nanoparticles in an array can introduce ultrasharp lattice plasmon resonances with out-of-plane charge oscillations that are tolerant to lateral strain. By patterning these nanoparticles onto an elastomeric slab surrounded by liquid gain, we realized reversible, tunable nanolasing with high strain sensitivity and no hysteresis. Our semiquantum modeling demonstrates that lasing build-up occurs at the hybrid quadrupole electromagnetic hot spots, which provides a route toward mechanical modulation of light-matter interactions on the nanoscale.

16.
Opt Express ; 26(8): 9515-9527, 2018 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-29715901

RESUMEN

We present a hybrid fiber link combining effective optical frequency transfer and evaluation of performances with a self-synchronized two-way comparison. It enables us to detect the round-trip fiber noise and each of the forward and backward one-way fiber noises simultaneously. The various signals acquired with this setup allow us to study quantitatively several properties of optical fiber links. We check the reciprocity of the accumulated noise forth and back over a bi-directional fiber to the level of 3.1(±3.9) × 10-20 based on a 160000s continuous data. We also analyze the noise correlation between two adjacent fibers and show the first experimental evidence of interferometric noise at very low Fourier frequency. We estimate redundantly and consistently the stability and accuracy of the transferred optical frequency over 43 km at 4 × 10-21 level after 16 days of integration and demonstrate that a frequency comparison with instability as low as 8 × 10-18 would be achievable with uni-directional fibers in urban area.

17.
Amino Acids ; 50(11): 1583-1594, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-30105541

RESUMEN

Previously we have demonstrated transglutaminase 2 (TGase 2) inhibition abrogated renal cell carcinoma (RCC) using GK921 (3-(phenylethynyl)-2-(2-(pyridin-2-yl)ethoxy)pyrido[3,2-b]pyrazine), although the mechanism of TGase 2 inhibition remains unsolved. Recently, we found that the increase of TGase 2 expression is required for p53 depletion in RCC by transporting the TGase 2 (1-139 a.a)-p53 complex to the autophagosome, through TGase 2 (472-687 a.a) binding p62. In this study, mass analysis revealed that GK921 bound to the N terminus of TGase 2 (81-116 a.a), which stabilized p53 by blocking TGase 2 binding. This suggests that RCC survival can be stopped by p53-induced cell death through blocking the p53-TGase 2 complex formation using GK921. Although GK921 does not bind to the active site of TGase 2, GK921 binding to the N terminus of TGase 2 also inactivated TGase 2 activity through acceleration of non-covalent self-polymerization of TGase 2 via conformational change. This suggests that TGase 2 has an allosteric binding site (81-116 a.a) which changes the conformation of TGase 2 enough to accelerate inactivation through self-polymer formation.


Asunto(s)
Carcinoma de Células Renales/enzimología , Proteínas de Unión al GTP/metabolismo , Neoplasias Renales/enzimología , Proteínas de Neoplasias/metabolismo , Transglutaminasas/metabolismo , Regulación Alostérica , Carcinoma de Células Renales/tratamiento farmacológico , Línea Celular Tumoral , Proteínas de Unión al GTP/antagonistas & inhibidores , Proteínas de Unión al GTP/genética , Células HEK293 , Humanos , Neoplasias Renales/tratamiento farmacológico , Proteínas de Neoplasias/antagonistas & inhibidores , Proteínas de Neoplasias/genética , Dominios Proteicos , Proteína Glutamina Gamma Glutamiltransferasa 2 , Pirazinas/farmacología , Transglutaminasas/antagonistas & inhibidores , Transglutaminasas/genética
18.
Langmuir ; 34(51): 15749-15753, 2018 12 26.
Artículo en Inglés | MEDLINE | ID: mdl-30507204

RESUMEN

Three-dimensional (3D) hierarchical wrinkles can be generated on prestrained thermoplastic substrates by sequential cycles of skin layer growth followed by the release of prestrain. However, no mechanics models have explained the formation of multigenerational nanostructures using this nanofabrication process. This article describes an analytical model that can represent multiscale wrinkles with arbitrary numbers of generations. Structural features including wrinkle wavelengths and amplitudes on the nanoscale that are predicted by minimizing the total deformation energy of the system. The calculated wavelengths in each generation are in good agreement with experiment. Our mathematical approach provides design principles for achieving multigenerational hierarchical structures.

19.
Proc Natl Acad Sci U S A ; 112(40): 12372-7, 2015 Oct 06.
Artículo en Inglés | MEDLINE | ID: mdl-26392564

RESUMEN

Intercellular bridges are a conserved feature of spermatogenesis in mammalian germ cells and derive from arresting cell abscission at the final stage of cytokinesis. However, it remains to be fully understood how germ cell abscission is arrested in the presence of general cytokinesis components. The TEX14 (testis-expressed gene 14) protein is recruited to the midbody and plays a key role in the inactivation of germ cell abscission. To gain insights into the structural organization of TEX14 at the midbody, we have determined the crystal structures of the EABR [endosomal sorting complex required for transport (ESCRT) and ALIX-binding region] of CEP55 bound to the TEX14 peptide (or its chimeric peptides) and performed functional characterization of the CEP55-TEX14 interaction by multiexperiment analyses. We show that TEX14 interacts with CEP55-EABR via its AxGPPx3Y (Ala793, Gly795, Pro796, Pro797, and Tyr801) and PP (Pro803 and Pro804) sequences, which together form the AxGPPx3YxPP motif. TEX14 competitively binds to CEP55-EABR to prevent the recruitment of ALIX, which is a component of the ESCRT machinery with the AxGPPx3Y motif. We also demonstrate that a high affinity and a low dissociation rate of TEX14 to CEP55, and an increase in the local concentration of TEX14, cooperatively prevent ALIX from recruiting ESCRT complexes to the midbody. The action mechanism of TEX14 suggests a scheme of how to inactivate the abscission of abnormal cells, including cancer cells.


Asunto(s)
Células Germinativas/metabolismo , Testículo/metabolismo , Factores de Transcripción/química , Factores de Transcripción/metabolismo , Secuencia de Aminoácidos , Animales , Sitios de Unión/genética , Proteínas de Ciclo Celular/química , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Cristalografía por Rayos X , Expresión Génica , Células HeLa , Humanos , Espectroscopía de Resonancia Magnética , Masculino , Ratones Endogámicos C57BL , Modelos Moleculares , Datos de Secuencia Molecular , Mutación , Proteínas Nucleares/química , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Unión Proteica , Estructura Terciaria de Proteína , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Espermatogénesis/genética , Testículo/citología , Factores de Transcripción/genética
20.
Int J Mol Sci ; 19(2)2018 Jan 27.
Artículo en Inglés | MEDLINE | ID: mdl-29382046

RESUMEN

Intrinsically disordered proteins (IDPs) represent approximately 30% of the human genome and play key roles in cell proliferation and cellular signaling by modulating the function of target proteins via protein-protein interactions. In addition, IDPs are involved in various human disorders, such as cancer, neurodegenerative diseases, and amyloidosis. To understand the underlying molecular mechanism of IDPs, it is important to study their structural features during their interactions with target proteins. However, conventional biochemical and biophysical methods for analyzing proteins, such as X-ray crystallography, have difficulty in characterizing the features of IDPs because they lack an ordered three-dimensional structure. Here, we present biochemical and biophysical studies on nucleolar phosphoprotein 140 (Nopp140), which mostly consists of disordered regions, during its interaction with casein kinase 2 (CK2), which plays a central role in cell growth. Surface plasmon resonance and electron paramagnetic resonance studies were performed to characterize the interaction between Nopp140 and CK2. A single-molecule fluorescence resonance energy transfer study revealed conformational change in Nopp140 during its interaction with CK2. These studies on Nopp140 can provide a good model system for understanding the molecular function of IDPs.


Asunto(s)
Proteínas Intrínsecamente Desordenadas/química , Simulación de Dinámica Molecular , Proteínas Nucleares/química , Fosfoproteínas/química , Animales , Quinasa de la Caseína II/metabolismo , Transferencia Resonante de Energía de Fluorescencia/métodos , Humanos , Proteínas Intrínsecamente Desordenadas/metabolismo , Espectroscopía de Resonancia Magnética/métodos , Proteínas Nucleares/metabolismo , Fosfoproteínas/metabolismo , Unión Proteica
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