• Title/Summary/Keyword: Molecular Recognition

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Novel function of stabilin-2 in myoblast fusion: the recognition of extracellular phosphatidylserine as a "fuse-me" signal

  • Kim, Go-Woon;Park, Seung-Yoon;Kim, In-San
    • BMB Reports
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    • v.49 no.6
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    • pp.303-304
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    • 2016
  • Myoblast fusion is important for skeletal muscle formation. Even though the knowledge of myoblast fusion mechanism has accumulated over the years, the initial signal of fusion is yet to be elucidated. Our study reveals the novel function of a phosphatidylserine (PS) receptor, stabilin-2 (Stab2), in the modulation of myoblast fusion, through the recognition of PS exposed on myoblasts. During differentiation of myoblasts, Stab2 expression is higher than other PS receptors and is controlled by calcineurin/NFAT signaling on myoblasts. The forced expression of Stab2 results in an increase in myoblast fusion; genetic ablation of Stab2 in mice causes a reduction in muscle size, as a result of impaired myoblast fusion. After muscle injury, muscle regeneration is impaired in Stab2-deficient mice, resulting in small myofibers with fewer nuclei, which is due to reduction of fusion rather than defection of myoblast differentiation. The fusion-promoting role of Stab2 is dependent on its PS-binding motif, and the blocking of PS-Stab2 binding impairs cell-cell fusion on myoblasts. Given our previous finding that Stab2 recognizes PS exposed on apoptotic cells for sensing as an "eat-me" signal, we propose that PS-Stab2 binding is required for sensing of a "fuse-me" signal as the initial signal of myoblast fusion.

Site-Directed Mutagenesis Studies with Restriction Endonuclease EcoRV to Identify the Role of Ile91 in Recognition and Catalysis

  • Moon, Byung-Jo;Vipond, I. Barry;Halford, Stephen E.
    • BMB Reports
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    • v.29 no.2
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    • pp.99-104
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    • 1996
  • Site-directed substitutions were made to change the Ile91 of restriction endonuclease EcoRV to either Val, Ala or Gly to identify the role of Ile91 in recognition and catalysis, since substitution of Ile91 with Leu afforded dramatic effects on the activity and properties of restriction endonuclease EcoRV. These changes alter the size of the hydrophobic side chain at position 91 and thus might have revealed the reason for the altered phenotype of Ile91Leu. However, the properties of Ile91Val and Ile91Ala mutants were much like wild type EcoRV, in both activity and metal ion preference. Ile91Gly had very little activity with either $Mg^{2+}$ or $Mn^{2+}$ as cofactors. To try to understand the unusual $Mn^{2+}$ profile of the Ile91Leu mutant, two double mutants, Ile91Leu;Asp90Asn and Ile91Leu;Glu45Met were created. Both double mutants were seriously disabled by the second amino acid change. Ile91Leu;Glu45Met had some residual activity in the $Mn^{2+}$ reaction buffer, whereas the Ile91Leu;Asp90Asn displayed no detectable activity.

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Immunomodulating Activity of Fungal ${\beta}-Glucan$ through Dectin-1 and Toll-like Receptor on Murine Macrophage

  • Kim, Ha-Won
    • 한국약용작물학회:학술대회논문집
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    • 2006.11a
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    • pp.103-115
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    • 2006
  • [ ${\beta}-Glucan$ ] is a glucose polymer that has linkage of ${\beta}-(1,3)$, -(1,4) and -(1,6). As exclusively found in fungal and bacterial cell wall, not in animal, ${\beta}-glucans$ are recognized by innate immune system. Dendritic cells (DC) or macrophages possesses pattern recognition molecule (PRM) for binding ${\beta}-glucans$ as pathogen-associated molecular pattern (PAMP). Recently ${\beta}-glucans$ receptor was cloned from DC and named as dectin-l which belongs to type II C-type lectin family. Human dectin-l is consisted of 7 exons and 6 introns. The polypeptide of dectin-l has 247 amino acids and has cytoplasmic, transmembrane, stalk and carbohydrate recognition domains. Dectin-l could recognize variety of beta-l,3 and/or beta-l,6 glucan linkages, but not alpha-glucans. In our macrophage cell line culture system, dectin-l mRNA was detected in RA W264.7 cells by reverse transcription-polymerase chain reaction (RT-PCR). Dectin-l was also detected in the murine organs of spleen, thymus, lung and intestines. Treatment of RA W264.7 cells with ${\beta}-glucans$ of Ganoderma lucidum (GLG) resulted in increased expression of IL-6 and $TNF-{\alpha}$ in the presence of LPS. However, GLG alone did not increase IL-6 nor $TNF-{\alpha}$ These results suggest that receptor dectin-l cooperate with CD14 to activate signal transduction that is very critical in immunoresponse.

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Molecular cloning and expression analysis of a C-type lectin in the rock bream, Oplegnathus fasciatus

  • Kwon, Mun-Gyeong;Kim, Ju-Won;Park, Myoung-Ae;Hwang, Jee-Youn;Park, Hyung-Jun;Park, Chan-Il
    • Journal of fish pathology
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    • v.25 no.1
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    • pp.11-20
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    • 2012
  • C-type lectins are crucial for pathogen recognition, innate immunity, and cell-cell interactions. In this study, a C-type lectin gene was cloned from the rock bream. The full-length RbCTL cDNA was 729 bp with a 429 bp ORF encoding a 164-residue protein. The deduced amino acid sequence of RbCTL had all of the conserved features crucial for its fundamental structure, including the four cysteine residues involved in sulfide bridge formation and potential $Ca^2+$/carbohydrate-binding sites. RbCTL contains a signal peptide one single carbohydrate recognition domain. It showed 29.4% similarity to the C-type lectin of rainbow trout. RbCTL mRNA was predominately expressed in gill and head-kidney tissue and expressed less in peripheral blood leukocytes, trunk-kidney, spleen, liver, intestine and muscle. Expression of RbCTL was differentially upregulated in rock bream stimulated with LPS, Con A/PMA and poly I:C.

In Vitro Selection of Hammerhead Ribozymes with Optimized Stems I and III

  • Sim, So-Yeong;Kim, Se-Mi;Kim, Ha-Dong;Ahn, Jeong-Keun;Lee, Young-Hoon;Cho, Bong-Rae;Park, In-Won
    • BMB Reports
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    • v.31 no.2
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    • pp.177-182
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    • 1998
  • A pool of cis-acting hammerhead ribozymes randomized in their substrate recognition sequences was constructed. A variety of active cis-acting ribozymes which had various structures of stems I and III was selected from the pool by in vitro selection. The selected ribozymes were cloned and sequenced. The relationship between the cleavage efficiency and base-pairing in stems I and III of the selected ribozymes was investigated. The ribozymes with the smaller difference in folding energies between the active conformation and the stable but inactive conformation showed a tendency to have the better cleavage efficiency. The optimum length of stem I was 5 or 6 bases while the longer stem III, in general, appeared to be required for efficient cleavage. The specificity of the ribozyme reaction is discussed in terms of the length of stems I and III.

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The Arg and Lys-Rich Motif in the TSPY Gene of Humans and Japanese Monkeys (Macaca fuscata) is Conserved in Various Primate Species

  • Kim, Heui-Soo;Takashi Kageyama;Osamu Takenaka
    • Journal of Life Science
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    • v.10 no.1
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    • pp.37-39
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    • 2000
  • Testis-specific protein Y(TSPY) is thought to play an important role during spermatogenesis in primates. The Arg and Lys-rich region of TSPY was implicated as a potential DNA binding site in the human and Japanese monkey. In the study, we investigated this further through looking at the putative amino acid sequences of Arg and Lys-rich region of TSPY gene from seven species of gibbons, five species of Old World monkeys and five species of New World monkeys. A comparison with those of the human and Japanese monkey revealed that the Arg and Lys-rich motif was hightly conserved in various primates. This finding suggests that a possible role for the Arg and Lys-rich motif in primate TSPY is DNA recognition. The functional implications for TSPY are discussed in the light of this and previous findings.

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Mechanism of amyloidogenesis: nucleation-dependent fibrillation versus double-concerted fibrillation

  • Bhak, Ghi-Bom;Choe, Young-Jun;Paik, Seung-R.
    • BMB Reports
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    • v.42 no.9
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    • pp.541-551
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    • 2009
  • Amyloidogenesis defines a condition in which a soluble and innocuous protein turns to insoluble protein aggregates known as amyloid fibrils. This protein suprastructure derived via chemically specific molecular self-assembly process has been commonly observed in various neurodegenerative disorders such as Alzheimer's, Parkinson's, and Prion diseases. Although the major culprit for the cellular degeneration in the diseases remains unsettled, amyloidogenesis is considered to be etiologically involved. Recent recognition of fibrillar polymorphism observed mostly from in vitro amyloidogeneses may indicate that multiple mechanisms for the amyloid fibril formation would be operated. Nucleation-dependent fibrillation is the prevalent model for assessing the self-assembly process. Following thermodynamically unfavorable seed formation, monomeric polypeptides bind to the seeds by exerting structural adjustments to the template, which leads to accelerated amyloid fibril formation. In this review, we propose another in vitro model of amyloidogenesis named double-concerted fibrillation. Here, two consecutive assembly processes of monomers and subsequent oligomeric species are responsible for the amyloid fibril formation of $\alpha$-synuclein, a pathological component of Parkinson's disease, following structural rearrangement within the oligomers which then act as a growing unit for the fibrillation.

Molecular Dynamics Simulation and Density Functional Theory Investigation for Thiacalix[4]biscrown and its Complexes with Alkali-Metal Cations

  • Hong, Joo-Yeon;Lee, Che-Wook;Ham, Si-Hyun
    • Bulletin of the Korean Chemical Society
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    • v.31 no.2
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    • pp.453-456
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    • 2010
  • The structural and energetic preferences of thiacalix[4]biscrown-5 with and without alkali metal ions ($Na^+$, $K^+$, $Rb^+$, and $Cs^+$) have been theoretically investigated for the first time using molecular dynamic (MD) simulations and density functional theory (MPWB1K/6-31G(d)//B3LYP/6-31G(d)) methods. The formation of the metal ion complex by the host is mainly driven by the electrostatic attraction between crown-5 oxygens and a cation together with the minor contribution of the cation-$\pi$ interaction between two facing phenyl rings around the cation. The computed binding energies and the atomic charge distribution analysis for the metal binding complexes indicate the selectivity toward a potassium ion. The theoretical results herein explain the experimentally observed extractability order by this host towards various alkali metal ions. The physical nature and the driving forces for cation recognition by this host are discussed in detail.

A Maximum Entropy-Based Bio-Molecular Event Extraction Model that Considers Event Generation

  • Lee, Hyoung-Gyu;Park, So-Young;Rim, Hae-Chang;Lee, Do-Gil;Chun, Hong-Woo
    • Journal of Information Processing Systems
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    • v.11 no.2
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    • pp.248-265
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    • 2015
  • In this paper, we propose a maximum entropy-based model, which can mathematically explain the bio-molecular event extraction problem. The proposed model generates an event table, which can represent the relationship between an event trigger and its arguments. The complex sentences with distinctive event structures can be also represented by the event table. Previous approaches intuitively designed a pipeline system, which sequentially performs trigger detection and arguments recognition, and thus, did not clearly explain the relationship between identified triggers and arguments. On the other hand, the proposed model generates an event table that can represent triggers, their arguments, and their relationships. The desired events can be easily extracted from the event table. Experimental results show that the proposed model can cover 91.36% of events in the training dataset and that it can achieve a 50.44% recall in the test dataset by using the event table.

Roles of Galectin-7 in Cancer

  • Kaur, Manpreet;Kaur, Tarnjeet;Kamboj, Sukhdev Singh;Singh, Jatinder
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.2
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    • pp.455-461
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    • 2016
  • Galectins are ${\beta}$-galactoside binding lectins that contain one or more carbohydrate recognition domains. As a consequence of sugar-binding properties, galectins exhibit a variety of interactions with glycoproteins, thus playing important roles in various pathological processes. A number of studies have shown roles of galectins in cancer. Galectin-7 is a prototype member of the galectin family implicated in epithelial stratification and cell migration. It can act as a potent dual regulator in different types of cancer. Galectin-7 may contribute either to neoplastic transformation and tumour progression through regulation of cell growth, cell cycle, angiogenesis, apoptosis and cell migration or may have a protective effect in cancer depending on the tissue type. A perusal of the literature indicates particular roles of galectin-7 in carcinomas and melanomas, while contributions await greater exploration in other types of cancers including sarcomas and leukemia. This review collectively summarizes available literature on expression and roles of galectin-7 in different cancers.