• Title/Summary/Keyword: membrane targeting

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Multilevel Precision-Based Rational Design of Chemical Inhibitors Targeting the Hydrophobic Cleft of Toxoplasma gondii Apical Membrane Antigen 1 (AMA1)

  • Vetrivel, Umashankar;Muralikumar, Shalini;Mahalakshmi, B;K, Lily Therese;HN, Madhavan;Alameen, Mohamed;Thirumudi, Indhuja
    • Genomics & Informatics
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    • v.14 no.2
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    • pp.53-61
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    • 2016
  • Toxoplasma gondii is an intracellular Apicomplexan parasite and a causative agent of toxoplasmosis in human. It causes encephalitis, uveitis, chorioretinitis, and congenital infection. T. gondii invades the host cell by forming a moving junction (MJ) complex. This complex formation is initiated by intermolecular interactions between the two secretory parasitic proteins-namely, apical membrane antigen 1 (AMA1) and rhoptry neck protein 2 (RON2) and is critically essential for the host invasion process. By this study, we propose two potential leads, NSC95522 and NSC179676 that can efficiently target the AMA1 hydrophobic cleft, which is a hotspot for targeting MJ complex formation. The proposed leads are the result of an exhaustive conformational search-based virtual screen with multilevel precision scoring of the docking affinities. These two compounds surpassed all the precision levels of docking and also the stringent post docking and cumulative molecular dynamics evaluations. Moreover, the backbone flexibility of hotspot residues in the hydrophobic cleft, which has been previously reported to be essential for accommodative binding of RON2 to AMA1, was also highly perturbed by these compounds. Furthermore, binding free energy calculations of these two compounds also revealed a significant affinity to AMA1. Machine learning approaches also predicted these two compounds to possess more relevant activities. Hence, these two leads, NSC95522 and NSC179676, may prove to be potential inhibitors targeting AMA1-RON2 complex formation towards combating toxoplasmosis.

Recent Development of Pervaporation in Japan

  • Mizoguchi, Kensaku
    • Proceedings of the Membrane Society of Korea Conference
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    • 1996.03a
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    • pp.25-43
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    • 1996
  • In general, membrane technology in Japan has remarkably developed in these 20 years. Especially, ones treating water is now in high level and seems to be matured. Water shortage of last summer was a new stimulus for promoting membrane research works. The researches are now extending to more precise separation of, for example, isomer and proteins. In such cases, not only polymeric materials but also ceramic or carbon ones are attempted. Concerning pervaporation (PV), water permselective membranes (GFT) are in practical use, PV research works are now concentrating on separation of new targeting substances. Here, I'd like to introduce, first of all, the outline of membrane technology in Japan (not limited to PV), and then of PV research works.

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The In Vitro Translocation of Escherichia coli Ribose-binding Protein via Various Targeting Routes

  • Lee, Byoung-Chul;Kim, Hyoung-Nan;Hwang, Yong-Il
    • BMB Reports
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    • v.34 no.2
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    • pp.118-122
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    • 2001
  • The translocation of ribose-binding protein (RBP) into the inverted membrane vesicles (IMV) of Escherichia coli and eukaryotic microsomes was studied using the in vitro translation/translocation system. It was found that RBP was translocated into heterologous eukaryotic microsomes co-translationally, as well as post-translationally However, RBP was translocated only past-translationally into IMV. Degradation fragments of RBP with the molar mass of 14 and 16 kDa were produced during the translocation into IMV However, the amount of the degradation products decreased and the mature form of RBP appeared in the presence of phenylmethylsulfonyl fluoride (PMSF). PMSF and GTP accelerated the translocation of RBF It was also found that SecB enhanced the post-translational translocation of RBP It appears that RBP is translocated via at least two targeting paths.

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Antimicrobial Peptides (AMPs) with Dual Mechanisms: Membrane Disruption and Apoptosis

  • Lee, Juneyoung;Lee, Dong Gun
    • Journal of Microbiology and Biotechnology
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    • v.25 no.6
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    • pp.759-764
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    • 2015
  • Antimicrobial peptides (AMPs) are one of the critical components in host innate immune responses to imbalanced and invading microbial pathogens. Although the antimicrobial activity and mechanism of action have been thoroughly investigated for decades, the exact biological properties of AMPs are still elusive. Most AMPs generally exert the antimicrobial effect by targeting the microbial membrane, such as barrel stave, toroidal, and carpet mechanisms. Thus, the mode of action in model membranes and the discrimination of AMPs to discrepant lipid compositions between mammalian cells and microbial pathogens (cell selectivity) have been studied intensively. However, the latest reports suggest that not only AMPs recently isolated but also well-known membrane-disruptive AMPs play a role in intracellular killing, such as apoptosis induction. In this mini-review, we will review some representative AMPs and their antimicrobial mechanisms and provide new insights into the dual mechanism of AMPs.

Dual function of MG53 in membrane repair and insulin signaling

  • Tan, Tao;Ko, Young-Gyu;Ma, Jianjie
    • BMB Reports
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    • v.49 no.8
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    • pp.414-423
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    • 2016
  • MG53 is a member of the TRIM-family protein that acts as a key component of the cell membrane repair machinery. MG53 is also an E3-ligase that ubiquinates insulin receptor substrate-1 and controls insulin signaling in skeletal muscle cells. Since its discovery in 2009, research efforts have been devoted to translate this basic discovery into clinical applications in human degenerative and metabolic diseases. This review article highlights the dual function of MG53 in cell membrane repair and insulin signaling, the mechanism that underlies the control of MG53 function, and the therapeutic value of targeting MG53 function in regenerative medicine.

Deciphering the role of a membrane-targeting domain in assisting endosomal and autophagic membrane localization of a RavZ protein catalytic domain

  • Park, Jui-Hee;Lee, Seung-Hwan;Park, Sang-Won;Jun, Yong-Woo;Kim, Kunhyung;Jeon, Pureum;Kim, Myungjin;Lee, Jin-A;Jang, Deok-Jin
    • BMB Reports
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    • v.54 no.2
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    • pp.118-123
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    • 2021
  • The bacterial effector protein RavZ from a pathogen can impair autophagy in the host by delipidating the mammalian autophagy-related gene 8 (mATG8)-phosphatidylethanolamine (PE) on autophagic membranes. In RavZ, the membrane-targeting (MT) domain is an essential function. However, the molecular mechanism of this domain in regulating the intracellular localization of RavZ in cells is unclear. In this study, we found that the fusion of the green fluorescent protein (GFP) to the MT domain of RavZ (GFP-MT) resulted in localization primarily to the cytosol and nucleus, whereas the GFP-fused duplicated-MT domain (GFP-2xMT) localized to Rab5- or Rab7-positive endosomes. Similarly, GFP fusion to the catalytic domain (CA) of RavZ (GFP-CA) resulted in localization primarily to the cytosol and nucleus, even in autophagy-induced cells. However, by adding the MT domain to GFP-CA (GFP-CA-MT), the cooperation of MT and CA led to localization on the Rab5-positive endosomal membranes in a wortmannin-sensitive manner under nutrient-rich conditions, and to autophagic membranes in autophagy-induced cells. In autophagic membranes, GFP-CA-MT delipidated overexpressed or endogenous mATG8-PE. Furthermore, GFP-CA△α3-MT, an α3 helix deletion within the CA domain, failed to localize to the endosomal or autophagic membranes and could not delipidate overexpressed mATG8-PE. Thus, the CA or MT domain alone is insufficient for stable membrane localization in cells, but the cooperation of MT and CA leads to localization to the endosomal and autophagic membranes. In autophagic membranes, the CA domain can delipidate mATG8-PE without requiring substrate recognition mediated by LC3-interacting region (LIR) motifs.

A Comparison of the Appearance in Implant Success according to Membrane Type during GBR(Guided Bone Regeneration) (골유도 재생술식(GBR)시 차단막 종류에 따른 임플란트 결과 비교)

  • Lee, Sunmi;Kim, Jiyoung
    • Journal of The Korean Society of Integrative Medicine
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    • v.2 no.2
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    • pp.41-47
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    • 2014
  • Purpose : The aim was to compare the implant success rate according to membrane type through a clinical case of patients, who used bio-resorbable membrane and non-resorbable membrane. Methods : A survey was conducted targeting patients with the use of bio-resorbable membrane and non-resorbable membrane who visited H dental clinic in Busan for implant surgery and bone graft for 1 year from May 2010 to May 2011. A chart was made and surveyed for 100 people with non-resorbable membrane and for 75 people with bio-resorbable membrane. Results were compared. Results : 1. As for the measurement value of Periotest M${(R)}$, the value of -8~0 was measured with 92% in case of surgery by using non-resorbable membrane. The value of +1~+9 was measured with 8.0%. In case of surgery by using bio-resorbable membrane, Peiotest M(R) was measured with 78.7% as for the value of -8~0 and 16(21.3%) as for the value of +1~+9. In light of this, a case of using non-resorbable membrane was indicated to be higher(p=0.021) in success rate than a case of using bio-resorbable membrane. 2. As a result of periodontal conditions, namely, bleeding(p=0.914), swelling(p=0.500), inflammation(p=0.074), pain(p=0.571), and itch appearance(p=0.475) according to membrane type, all were insignificant. Conclusions : A case of using non-resorbable membrane is considered to be likely to be more effective than using bio-resorbable membrane during GBR(Guided Bone Regeneration) with the use of membrane in implant surgery.

Glyco-engineering strategies for the development of therapeutic enzymes with improved efficacy for the treatment of lysosomal storage diseases

  • Oh, Doo-Byoung
    • BMB Reports
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    • v.48 no.8
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    • pp.438-444
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    • 2015
  • Lysosomal storage diseases (LSDs) are a group of inherent diseases characterized by massive accumulation of undigested compounds in lysosomes, which is caused by genetic defects resulting in the deficiency of a lysosomal hydrolase. Currently, enzyme replacement therapy has been successfully used for treatment of 7 LSDs with 10 approved therapeutic enzymes whereas new approaches such as pharmacological chaperones and gene therapy still await evaluation in clinical trials. While therapeutic enzymes for Gaucher disease have N-glycans with terminal mannose residues for targeting to macrophages, the others require N-glycans containing mannose-6-phosphates that are recognized by mannose-6-phosphate receptors on the plasma membrane for cellular uptake and targeting to lysosomes. Due to the fact that efficient lysosomal delivery of therapeutic enzymes is essential for the clearance of accumulated compounds, the suitable glycan structure and its high content are key factors for efficient therapeutic efficacy. Therefore, glycan remodeling strategies to improve lysosomal targeting and tissue distribution have been highlighted. This review describes the glycan structures that are important for lysosomal targeting and provides information on recent glyco-engineering technologies for the development of therapeutic enzymes with improved efficacy. [BMB Reports 2015; 48(8): 438-444]

On the New Design of Liquid Dome Chair in Membrane Type LNG Carrier (멤브레인형 LNG선박의 리퀴드 돔 체어 구조개발)

  • Kim, Jeong-Hwan;Kim, Yooil
    • Journal of the Society of Naval Architects of Korea
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    • v.54 no.5
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    • pp.361-367
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    • 2017
  • A membrane type LNG cargo tank is equipped with a pump tower and a liquid dome for loading and unloading of LNG. However, the membrane running continuously on the tank wall to prevent leakage of LNG is interrupted by the liquid dome, hence care should be taken in the design of liquid dome and its substructures. In case of GTT NO96 membrane type cargo containment system, chair structure is arranged along the periphery of the liquid dome targeting to support the membrane which is exposed to the both hull girder and thermal load. This paper proposes a new and simple chair structure, which outperforms traditional design from productivity point of view maintaining same level of structural safety. Strength assessment on the new design was performed to guarantee the structural safety of the new design, which includes strength, fatigue and crack propagation analysis.