• Molecules and Cells
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• 제44권5호
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• pp.342-355
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• 2021

The microphthalmia-associated transcription factor family (MiT family) proteins are evolutionarily conserved transcription factors that perform many essential biological functions. In mammals, the MiT family consists of MITF (microphthalmia-associated transcription factor or melanocyte-inducing transcription factor), TFEB (transcription factor EB), TFE3 (transcription factor E3), and TFEC (transcription factor EC). These transcriptional factors belong to the basic helix-loop-helix-leucine zipper (bHLH-LZ) transcription factor family and bind the E-box DNA motifs in the promoter regions of target genes to enhance transcription. The best studied functions of MiT proteins include lysosome biogenesis and autophagy induction. In addition, they modulate cellular metabolism, mitochondria dynamics, and various stress responses. The control of nuclear localization via phosphorylation and dephosphorylation serves as the primary regulatory mechanism for MiT family proteins, and several kinases and phosphatases have been identified to directly determine the transcriptional activities of MiT proteins. In different immune cell types, each MiT family member is shown to play distinct or redundant roles and we expect that there is far more to learn about their functions and regulatory mechanisms in host defense and inflammatory responses.

• Molecules and Cells
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• 제42권8호
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• pp.589-596
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• 2019

${\beta}Pix$ is a guanine nucleotide exchange factor for the Rho family small GTPases, Rac1 and Cdc42. It is known to regulate focal adhesion dynamics and cell migration. However, the in vivo role of ${\beta}Pix$ is currently not well understood. Here, we report the production and characterization of ${\beta}Pix$-KO mice. Loss of ${\beta}Pix$ results in embryonic lethality accompanied by abnormal developmental features, such as incomplete neural tube closure, impaired axial rotation, and failure of allantois-chorion fusion. We also generated ${\beta}Pix$-KO mouse embryonic fibroblasts (MEFs) to examine ${\beta}Pix$ function in mouse fibroblasts. ${\beta}Pix$-KO MEFs exhibit decreased Rac1 activity, and defects in cell spreading and platelet-derived growth factor (PDGF)-induced ruffle formation and chemotaxis. The average size of focal adhesions is increased in ${\beta}Pix$-KO MEFs. Interestingly, ${\beta}Pix$-KO MEFs showed increased motility in random migration and rapid wound healing with elevated levels of MLC2 phosphorylation. Taken together, our data demonstrate that ${\beta}Pix$ plays essential roles in early embryonic development, cell spreading, and cell migration in fibroblasts.

• 한국자기공명학회논문지
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• 제23권1호
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• pp.26-32
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• 2019

${\alpha}B$-crystallin (${\alpha}BC$) is a member of a small heat-shock protein (sHSP) superfamily and plays a predominant role in cellular protein homeostasis network by rescuing misfolded proteins from irreversible aggregation. ${\alpha}BC$ assembles into dynamic and polydisperse high molecular weight complexes containing 12 to 48 monomers; this variable stereochemistry of ${\alpha}BC$ has been linked to quaternary subunit exchange and its chaperone activity. The chaperone activity of ${\alpha}BC$ poses great potential as therapeutic agents for various neurodegenerative diseases. In this mini-review, we briefly outline the recent advancement in structural characterization of ${\alpha}BCs$ and its potential role to inhibit protein misfolding and aggregation in various human diseases. In particular, nuclear magnetic resonance (NMR) spectroscopy and its complimentary techniques have contributed much to elucidate highly-dynamic nature of ${\alpha}BCs$, among which notable advancements are discussed in detail. We highlight the importance of resolving the structural details of various ${\alpha}BC$ oligomers, their quaternary dynamics, and structural heterogeneity.

• BMB Reports
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• 제54권1호
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• pp.2-11
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• 2021

Antibody-based therapeutics targeting the inhibitory receptors PD-1, PD-L1, or CTLA-4 have shown remarkable clinical progress on several cancers. However, most patients do not benefit from these therapies. Thus, many efforts are being made to identify new immune checkpoint receptor-ligand pathways that are alternative targets for cancer immunotherapies. Nectin and nectin-like molecules are widely expressed on several types of tumor cells and play regulatory roles in T- and NK-cell functions. TIGIT, CD226, CD96 and CD112R on lymphoid cells are a group of immunoglobulin superfamily receptors that interact with Nectin and nectin-like molecules with different affinities. These receptors transmit activating or inhibitory signals upon binding their cognate ligands to the immune cells. The integrated signals formed by their complex interactions contribute to regulating immune-cell functions. Several clinical trials are currently evaluating the efficacy of anti-TIGIT and anti-CD112R blockades for treating patients with solid tumors. However, many questions still need to be answered in order to fully understand the dynamics and functions of these receptor networks. This review addresses the rationale behind targeting TIGIT, CD226, CD96, and CD112R to regulate T- and NK-cell functions and discusses their potential application in cancer immunotherapy.

• 대한화학회지
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• 제64권6호
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• pp.345-349
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• 2020

금 표면 위에서 알칸싸이올 분자가 자기조립을 통해 단분자층을 만들 때 싸이올기가 화학 흡착을 못하고 알킬기가 물리 흡착을 하는 결함이 생길 수 있다. 이러한 결함은 열적 어닐링 과정으로 제거할 수 있음이 알려져 있다. 우리는 알칸싸이올 분자에 대한 이징 모형을 제시하고 단분자층 어닐링 과정의 몬테카를로 시뮬레이션에 적용하였다. 새로운 이징 모형은 선행 분자동역학 시뮬레이션에서 나타난 어닐링을 통한 단분자층의 결함 제거를 성공적으로 재현할 수 있었다.

• Bulletin of the Korean Chemical Society
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• 제12권2호
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• pp.214-219
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• 1991

To study the effect of solvents and counterions in Z-DNA crystal of d(5BrC-G-5BrC-G-5BrC-G), we performed the local energy analysis and then molecular dynamics simulations. Since counterions raise serious caging problems in crystal simulations, it is very important to search for the possible positions before simulations. For this purpose, the local energy analysis was done for the whole crystal volume. It is shown from our simulation that counterions along with water molecules play a bridging role to bind adjacent oligomers so as to form the crystal. In this crystal, each water molecule bound to Gua-N2H, either directly or indirectly, hydrates the adjacent anionic phosphate oxygen, and thus assists Gua to be in a syn position. From the simulation, the average root-mean-square deviation of allthe DNA heavy atom coordinates from the X-ray data is $0.99{\AA}$ . The bases are less deviated from the X-ray positions than the phosphates. The temperature factors from the simulation are consistent with those from the X-ray refinement, showing that the phosphates are more mobile than the bases.

• Bulletin of the Korean Chemical Society
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• 제5권4호
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• pp.162-167
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• 1984

Equilibrium and dynamical behaviors of an n-alkane poymer (decane) in solution have been investigated by a molecuar dynamics simulation method. The polymer is assumed to be a chain of elements $(CH_2)$ interconnected by bonds having a fixed bond length and bond angle, but esch bond of the polymer is allowed to execute hindered internal rotation. The calculation explicitly considers the molecular naturer of solvent by including the intermolecular interactions between slovent-solvent molecules and chain element-solvent molecule. We present the results of calculations on (1) equilibrium properties (the solvent molecule-chain element pair correlation function, chain element-chain element pair correlation function, the mean square end-to-end distance and the mean square radius of gyration of the polymer) and (2) dynamic properties (four different autocorrelation functions, namely, the autocorrelation functions for the end-to-end distance and the radius of gyration, and the velocity autocorrelation functions for the center of mass and the end point of the chain). We found that the physical properties of the polymer chain depends sensitively on temperature. Comparison of the present work with other authors' results is also presented.

• 식품과학과 산업
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• 제50권1호
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• pp.2-10
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• 2017

Human have eaten various traditional fermented foods for a numbers of million years for health benefit as well as survival. The beneficial effects of fermented foods have been resulted from complex microbial communications within the fermented foods. Therefore, the holistic approaches for individual identification and complete microbial profiling involved in their communications have been of interest to food microbiology fields. Microbiome is the ecological community of microorganisms that literally share our environments including foods as well as human body. However, due to the limitation of culture-dependent methods such as simple isolations of just culturable microorganisms, the culture-independent methods have been consistently developed, resulting in new light on the diverse non-culturable and hitherto unknown microorganisms, and even microbial communities in the fermented foods. For the culture-independent approaches, the food microbiome has been deciphered by employing various molecular analysis tools such as fluorescence in situ hybridization, quantitative PCR, and denaturing gradient gel-electrophoresis. More recently, next-generation-sequencing (NGS) platform-based microbiome analysis has been of interest, because NGS is a powerful analytical tool capable of resolving the microbiome in respect to community structures, dynamics, and activities. In this overview, the development status of analysis tools for the fermented food microbiome is covered and research trend for NGS-based food microbiome analysis is also discussed.

• Molecules and Cells
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• 제44권3호
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• pp.127-135
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• 2021

Since the introduction of RNA sequencing (RNA-seq) as a high-throughput mRNA expression analysis tool, this procedure has been increasingly implemented to identify cell-level transcriptome changes in a myriad of model systems. However, early methods processed cell samples in bulk, and therefore the unique transcriptomic patterns of individual cells would be lost due to data averaging. Nonetheless, the recent and continuous development of new single-cell RNA sequencing (scRNA-seq) toolkits has enabled researchers to compare transcriptomes at a single-cell resolution, thus facilitating the analysis of individual cellular features and a deeper understanding of cellular functions. Nonetheless, the rapid evolution of high throughput single-cell "omics" tools has created the need for effective hypothesis verification strategies. Particularly, this issue could be addressed by coupling cell engineering techniques with single-cell sequencing. This approach has been successfully employed to gain further insights into disease pathogenesis and the dynamics of differentiation trajectories. Therefore, this review will discuss the current status of cell engineering toolkits and their contributions to single-cell and genome-wide data collection and analyses.

• BMB Reports
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• 제54권12호
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• pp.626-631
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• 2021

Janus kinase 2 (JAK2), a non-receptor tyrosine kinase, is a critical component of cytokine and growth factor signaling pathways regulating hematopoietic cell proliferation. JAK2 mutations are associated with multiple myeloproliferative neoplasms. Although physiological and pathological functions of JAK2 in hematopoietic tissues are well-known, such functions of JAK2 in the nervous system are not well studied yet. The present study demonstrated that JAK2 could negatively regulate neuronal differentiation of mouse embryonic stem cells (ESCs). Depletion of JAK2 stimulated neuronal differentiation of mouse ESCs and activated glycogen synthase kinase 3β, Fyn, and cyclin-dependent kinase 5. Knockdown of JAK2 resulted in accumulation of GTP-bound Rac1, a Rho GTPase implicated in the regulation of cytoskeletal dynamics. These findings suggest that JAK2 might negatively regulate neuronal differentiation by suppressing the GSK-3β/Fyn/CDK5 signaling pathway responsible for morphological maturation.