• Title/Summary/Keyword: Ligand organization

검색결과 28건 처리시간 0.023초

Single and Dual Ligand Effects on Gene Expression Changes in Mouse Macrophage Cells

  • Choi Sang-Dun;Seo Jeong-Sun
    • Genomics & Informatics
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    • 제4권2호
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    • pp.57-64
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    • 2006
  • We identified differentially expressed genes in RAW264.7 cells in response to single and double ligand treatments (LPS, $IFN{\gamma}$, 2MA, LPS plus $IFN{\gamma}$, and LPS plus 2MA). The majority of the regulated transcripts responded additively to dual ligand treatment. However, a significant fraction responded in a non-additive fashion. Several cytokines showing non-additive transcriptional responses to dual ligand treatment also showed non-additive protein production/secretion responses in separately performed experiments. Many of the genes with non-additive responses to LPS plus 2MA showed enhanced responses and encoded pro-inflammatory proteins. LPS plus $IFN{\gamma}$ appeared to induce both non-additive enhancement and non-additive attenuation of gene expression. The affected genes were associated with a variety of biological functions. These experiments reveal both dependent and independent regulatory pathways and point out the specific nature of the regulatory interactions.

Investigation of Cell-Matrix Interactions Using a FRET Technique

  • Shahbuddin, Munira B.;Park, Hong-Hyun;Lee, Jae-Won;Park, So-Yeon;Lee, Kuen-Yong
    • Bulletin of the Korean Chemical Society
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    • 제30권8호
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    • pp.1817-1820
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    • 2009
  • Controlling cell-matrix interactions is critical in regulating cell phenotypes for tissue engineering applications. Cellular adhesion to synthetic extracellular matrices (ECMs) can be enhanced by introduction of adhesion ligands to the matrices. We tested the hypothesis that biophysical cues such as ligand organization in synthetic ECMs play an important role in modulating cell responses to the microenvironment. To investigate and monitor cell-matrix interactions, we used a fluorescence resonance energy transfer (FRET) technique with cell-interactive polymers generated by conjugating a peptide with the sequence of arginine-glycine-aspartic acid (RGD) to alginate hydrogels.

In-silico and structure-based assessment to evaluate pathogenicity of missense mutations associated with non-small cell lung cancer identified in the Eph-ephrin class of proteins

  • Shubhashish Chakraborty;Reshita Baruah;Neha Mishra;Ashok K Varma
    • Genomics & Informatics
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    • 제21권3호
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    • pp.30.1-30.13
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    • 2023
  • Ephs belong to the largest family of receptor tyrosine kinase and are highly conserved both sequentially and structurally. The structural organization of Eph is similar to other receptor tyrosine kinases; constituting the extracellular ligand binding domain, a fibronectin domain followed by intracellular juxtamembrane kinase, and SAM domain. Eph binds to respective ephrin ligand, through the ligand binding domain and forms a tetrameric complex to activate the kinase domain. Eph-ephrin regulates many downstream pathways that lead to physiological events such as cell migration, proliferation, and growth. Therefore, considering the importance of Eph-ephrin class of protein in tumorigenesis, 7,620 clinically reported missense mutations belonging to the class of variables of unknown significance were retrieved from cBioPortal and evaluated for pathogenicity. Thirty-two mutations predicted to be pathogenic using SIFT, Polyphen-2, PROVEAN, SNPs&GO, PMut, iSTABLE, and PremPS in-silico tools were found located either in critical functional regions or encompassing interactions at the binding interface of Eph-ephrin. However, seven were reported in nonsmall cell lung cancer (NSCLC). Considering the relevance of receptor tyrosine kinases and Eph in NSCLC, these seven mutations were assessed for change in the folding pattern using molecular dynamic simulation. Structural alterations, stability, flexibility, compactness, and solvent-exposed area was observed in EphA3 Trp790Cys, EphA7 Leu749Phe, EphB1 Gly685Cys, EphB4 Val748Ala, and Ephrin A2 Trp112Cys. Hence, it can be concluded that the evaluated mutations have potential to alter the folding pattern and thus can be further validated by in-vitro, structural and in-vivo studies for clinical management.

Characteristics in Molecular Vibrational Frequency Patterns between Agonists and Antagonists of Histamine Receptors

  • Oh, S. June
    • Genomics & Informatics
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    • 제10권2호
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    • pp.128-132
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    • 2012
  • To learn the differences between the structure-activity relationship and molecular vibration-activity relationship in the ligand-receptor interaction of the histamine receptor, 47 ligands of the histamine receptor were analyzed by structural similarity and molecular vibrational frequency patterns. The radial tree that was produced by clustering analysis of molecular vibrational frequency patterns shows its potential for the functional classification of histamine receptor ligands.

System-Wide Expression and Function of Olfactory Receptors in Mammals

  • Oh, S. June
    • Genomics & Informatics
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    • 제16권1호
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    • pp.2-9
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    • 2018
  • Olfactory receptors (ORs) in mammals are generally considered to function as chemosensors in the olfactory organs of animals. They are membrane proteins that traverse the cytoplasmic membrane seven times and work generally by coupling to heterotrimeric G protein. The OR is a G protein-coupled receptor that binds the guanine nucleotide-binding $G{\alpha}_{olf}$ subunit and the $G{\beta}{\gamma}$ dimer to recognize a wide spectrum of organic compounds in accordance with its cognate ligand. Mammalian ORs were originally identified from the olfactory epithelium of rat. However, it has been recently reported that the expression of ORs is not limited to the olfactory organ. In recent decades, they have been found to be expressed in diverse organs or tissues and even tumors in mammals. In this review, the expression and expected function of olfactory receptors that exist throughout an organism's system are discussed.

Folding of Coordination Polymers into Double-Stranded Helical Organization

  • Kim, Ho-Joong;Lee, Eun-Ji;Lee, Myong-Soo
    • 한국고분자학회:학술대회논문집
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    • 한국고분자학회 2006년도 IUPAC International Symposium on Advanced Polymers for Emerging Technologies
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    • pp.248-248
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    • 2006
  • The notable feature of the Cu(II) coordination polymer investigated here is its ability to self-assemble into a double-stranded helical structure with regular grooves along the helical axis, through the combination of metal-chloride dimeric interactions and repulsive interactions, as an organizing force. It is also remarkable that the double-stranded helices self-organize into a 2-D columnar structure in both the bulk state and aqueous solution. These results represent a unique example that weak metal-ligand bridging interactions can provide a useful strategy to construct stable double-stranded helical nanotubes.

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A Novel Type of Non-coding RNA, nc886, Implicated in Tumor Sensing and Suppression

  • Lee, Yong Sun
    • Genomics & Informatics
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    • 제13권2호
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    • pp.26-30
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    • 2015
  • nc886 (=vtRNA2-1, pre-miR-886, or CBL3) is a newly identified non-coding RNA (ncRNA) that represses the activity of protein kinase R (PKR). nc886 is transcribed by RNA polymerase III (Pol III) and is intriguingly the first case of a Pol III gene whose expression is silenced by CpG DNA hypermethylation in several types of cancer. PKR is a sensor protein that recognizes evading viruses and induces apoptosis to eliminate infected cells. Like viral infection, nc886 silencing activates PKR and induces apoptosis. Thus, the significance of the nc886:PKR pathway in cancer is to sense and eliminate pre-malignant cells, which is analogous to PKR's role in cellular innate immunity. Beyond this tumor sensing role, nc886 plays a putative tumor suppressor role as supported by experimental evidence. Collectively, nc886 provides a novel example how epigenetic silencing of a ncRNA contributes to tumorigenesis by controlling the activity of its protein ligand.

Molecular Vibration-Activity Relationship in the Agonism of Adenosine Receptors

  • Chee, Hyun Keun;Oh, S. June
    • Genomics & Informatics
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    • 제11권4호
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    • pp.282-288
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    • 2013
  • The molecular vibration-activity relationship in the receptor-ligand interaction of adenosine receptors was investigated by structure similarity, molecular vibration, and hierarchical clustering in a dataset of 46 ligands of adenosine receptors. The resulting dendrogram was compared with those of another kind of fingerprint or descriptor. The dendrogram result produced by corralled intensity of molecular vibrational frequency outperformed four other analyses in the current study of adenosine receptor agonism and antagonism. The tree that was produced by clustering analysis of molecular vibration patterns showed its potential for the functional classification of adenosine receptor ligands.