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Aggregate 2024年第3期5卷 275-289页

作者： Nadjib Kihal Phuong Trang Nguyen Ali Nazemi Andrea A.Greschner Marc A.Gauthier Steve Bourgault Department of Chemistry Universitédu QuébecàMontréalMontrealCanada 2Quebec Network for Research on Protein FunctionEngineering and Applications(PROTEO)QuebecCanada 3NanoQAM and Quebec Centre for Advanced MaterialsQCAMMontrealCanada 4Institut National de la Recherche Scientiﬁque(INRS)EMT Research CenterVarennesCanada

The deposition of insoluble proteinaceous aggregates in the form of amyloidﬁbrils within the extracellular space of tissues is associated with numerous *** development of molecular approaches to arrest amyloid formation and prevent cel-lular degeneration remains very challenging due to the complexity of the process of protein aggregation,which encompasses an inﬁnite array of conformations and quaternary *** biopolymers,such as glycosaminoglycans and RNAs,have been shown to modulate the self-assembly of amyloidogenic polypep-tides and to reduce the toxicity induced by the formation of oligomeric and/or pre-ﬁbrillar *** study evaluates the effects of double-stranded DNA(dsDNA)nanostructures(1D,2D,and 3D)on amyloid self-assembly,ﬁbril dis-aggregation,and the cytotoxicity associated with *** the islet amyloid polypeptide(IAPP)whose pancreatic accumulation is the hallmark of type 2 diabetes,it was observed that dsDNA nanostructures inhibit amyloid formation by inducing the formation of spherical complexes in which the peptide adopts a random coil ***,the DNA nanostructures showed a per-sistent ability to disassemble enzymatically and thermodynamically stable amyloidﬁbrils into nanoscale DNA/IAPP entities that are fully compatible withβ-pancreatic cells and are biodegradable by ***,dsDNA nanostructures avidly trapped highly toxic soluble oligomeric species in complete cell culture media and converted them into non-toxic binary ***,these results expose the potent modulatory effects of dsDNA on amyloidogenic pathways,and these DNA nanoscaffolds could be used as a source of inspiration for the design of molecules toﬁght amyloid-related disorders.

关键词： amyloid cytotoxicity DNA nanostructures islet amyloid polypeptide oligomers self-assembly

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Theoretical and experimental biology in one<br>—A symposium in honour of Professor Kuo-Chen Chou’s 50th anniversary and Professor Richard Giegé’s 40th anniversary of their scientific careers

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Journal of Biomedical Science and Engineering 2013年第4期6卷 435-442页

作者： Sheng-Xiang Lin Jacques Lapointe Department of Biochemistry Microbiology and Bioinformatics and PROTEO Laval University Quebec Canada Laboratory of Molecular Endocrinology and Oncology Research Center of Laval University Hospital Center (CHUQ-CHUL) and PROTEO Laval University Quebec Canada

It has been a dream that theoretical biology can be extensively applied in experimental biology to accelerate the understanding of the sophiscated movements in living organisms. A brave assay and an excellent example were represented by enzymology, in which the well-established physico-chemistry is used to describe, to fit, to predict and to improve enzyme reactions. Before the modern bioinformatics, the developments of the combination of theoretical biology and experimental biology have been mainly limited to various classic formulations. The systematic use of graphic rules by Prof. Kuo-Chen Chou and his co-workers has significantly facilitated to deal with complicated enzyme systems. With the recent fast progress of bioinformatics, prediction of protein structures and various protein attributes have been well established by Chou and co-workers, stimulating the experimental biology. For example, their recent method for predicting protein subcellular localization (one of the important attributes of proteins) has been extensively applied by scientific colleagues, yielding many new results with thousands of citations. The research by Prof. Chou is characterized by introducing novel physical concepts as well as powerful and elegant mathematical methods into important biomedical problems, a focus throughout his career, even when facing enormous difficulties. His efforts in 50 years have greatly helped us to realize the dream to make “theoretical and experimental biology in one”. Prof. Richard Giege is well known for his multi-disciplinary research combining physics, chemistry, enzymology and molecular biology. His major focus of study is on the identity of tRNAs and their interactions with aminoacyl-tRNA synthetases (aaRS), which are of critical importance to the fidelity of protein biosynthesis. He and his colleagues have carried out the first crystallization of a tRNA/aaRS complex, that between tRNAAsp and AspRS from yeast. The determination of the complex structure c

关键词： Theoretical Biology Experimental Biology Chou’s Graphic Rules in Enzymology Prediction of Protein Attributes Chou’s Invariance Theorem Macromolecular Crystallogenesis tRNA Identity on Aminoacylation Specificity Physico-Biochemistry

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*** binding properties of the C-terminal segment of retinol dehydrogenase 8

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Annals of Eye Science 2018年第1期 428-428页

作者： AndréHädicke Ana I.A.Coutinho François Otis Mustapha Lhor Line Cantin Manuel Prieto Normand Voyer Christian Salesse proteo and cuo-recherche Centre de recherche du CHU de Québec-UniversitéLavalHôpital St-SacrementQuébecCanada Centro Química-Física Molecular Instituto Superior TécnicoUniversidade de LisboaLisboaPortugal proteo and Dépt.Chimie FacultéSciences et génieUniversitéLavalQuébecCanada

Background:Retinol dehydrogenase 8(RDH8)is a 312-amino acid(aa)protein involved in the visual *** to the outer segment disk membranes of photoreceptors,it reduces all-trans-retinal to all-trans-retinol1 as one of the rate-limiting steps of the visual ***8 is a member of the short-chain dehydrogenase/reductase *** C-terminal segment allows its membrane-anchoring through the postulated presence of an amphipathicα-helix and of 1 to 3 acyl groups at positions 299,302 and *** secondary structure and membrane binding characteristics of RDH8 and its C-terminal segment have not yet been ***:To evaluate the membrane binding of RDH8,the full-length protein(aa 1-312),a truncated form(aa 1-296),its C-terminal segment(aa 281-312 and 297-312)as well as different additional variants of this segment were *** truncated protein binds membranes less efficiently than the full-length ***,the C-terminal segment of RDH8 is essential for the binding and has thus been further *** intrinsic fluorescence of tryptophan residues at positions 289 and 310 of the wild-type C-terminal segment of RDH8 and the mutants W289F,W310F and W310R have thus been used to determine their extent of binding to lipid vesicles and to monitor their local *** lipid vesicles composed of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine(POPC)or a mixture of POPC and 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-L-serine(POPS)were used to mimic the phospholipid content of the outer segment disk membranes of ***:An increase in fluorescence intensity and in fluorescence lifetime is observed upon increasing the concentration of lipid *** data allowed calculating values of partition coefficient of the C-terminal segment of RDH8 varying between Kp=1.1 E6 to 1.7 *** is noteworthy that the observation of a more intense shift to lower wavelengths upon membrane binding of the mutant W310R and W310F indicates a deeper inco

关键词： Peptide-membrane binding electrostatic interactions hydrophobic interactions fluorescence spectroscopy

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Administration frequency as well as dosage of PTH are associated with development of cortical porosity in ovariectomized rats

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Bone Research 2017年第2期5卷 109-122页

作者： Aya Takakura Ji-Won Lee Kyoko Hirano Yukihiro Isogai Toshinori Ishizuya Ryoko Takao-Kawabata Tadahiro Iimura Pharmaceuticals Research Center Asahi Kasei Pharma Corporation Shizuoka Japan Graduate School of Medicine Division of Analytical BioMedicine Ehime University Ehime Japan Division of Bio-Imaging Proteo-Science Center (PROS) Ehime University Ehime Japan Division of Analytical Bio-Medicine Advanced Research Support Center (ADRES) Ehime University Ehime Japan and Artificial Joint Integrated Center Ehime University Hospital Ehime Japan

To investigate whether the administration frequency of parathyroid hormone(PTH) is associated with the development of cortical porosity, this study established 15 dosage regimens of teriparatide [human PTH(1–34), TPTD] with four distinct concentrations and four distinct administration frequencies of TPTD to 16-week-old ovariectomized rats. Our analyses demonstrated that the bone mineral density, mechanical properties, and bone turnover were associated with the total amount of TPTD administered. Our observations further revealed that the cortical porosity was markedly developed as a result of an increased administration frequency with a lower concentration of total TPTD administration in our setting, although the highest concentration also induced cortical porosity. Deconvolution fluorescence tiling imaging on calcein-labeled undecalcified bone sections also demonstrated the development of cortical porosity to be closely associated with the bone site where periosteal bone formation took place. This site-specific cortical porosity involved intracortical bone resorption and an increased number and proximity of osteocytic lacunae,occasionally causing fused lacunae. Taken together, these findings suggested the involvement of local distinctions in the rate of bone growth that may be related to the site-specific mechanical properties in the development of cortical porosity induced by frequent and/or high doses of TPTD.

关键词： frequency Administration PTH

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Mechanism and evolution of multidomain aminoacyl-tRNA synthetases revealed by their inhibition by analogues of a reaction intermediate, and by properties of truncated forms

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Journal of Biomedical Science and Engineering 2013年第10期6卷 943-946页

作者： Jacques Lapointe Département de Biochimie de Microbiologie et de Bioinformatique Regroupement Québécois de Recherche sur la Fonction la Structure et L’ingénierie des Protéines (PROTEO) & Institut de Biologie Intégrative et des Systèmes (IBIS) Université Laval Québec Canada

Many enzymes which catalyze the conversion of large substrates are made of several structural domains belonging to the same polypeptide chain. Transfer RNA (tRNA), one of the substrates of the multidomain aminoacyl-tRNA synthetases (aaRS), is an L-shaped molecule whose size in one dimension is similar to that of its cognate aaRS. Crystallographic structures of aaRS/tRNA complexes show that these enzymes use several of their structural domains to interact with their cognate tRNA. This mini review discusses first some aspects of the evolution and of the flexibility of the pentadomain bacterial glutamyl-tRNA synthetase (GluRS) revealed by kinetic and interaction studies of complementary truncated forms, and then illustrates how stable analogues of aminoacyl-AMP intermediates have been used to probe conformational changes in the active sites of Escherichia coli GluRS and of the nondiscriminating aspartyl-tRNA synthetase (ND-AspRS) of Pseudomonas aeruginosa.

关键词： Multidomain Enzymes tRNA Aminoacyl-tRNA Synthetases Truncated Enzymes Steady-State Kinetics Inhibitors Mechanism Evolution

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Newfound Coding Potential of Transcripts Unveils Missing Members of Human Protein Communities

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Genomics, proteomics & Bioinformatics 2023年第3期21卷 515-534页

作者： Se´bastien Leblanc Marie *** Jean-Franc¸ois Jacques Amina M.Lekehal Andre´a Duclos Alexia Tremblay Alexis Bruggeman-Gascon Sondos Samandi Myle`ne Brunelle Alan A.Cohen Michelle S.Scott Xavier Roucou Department of Biochemistry and Functional Genomics Universite´de SherbrookeSherbrookeQC J1E 4K8Canada proteo Quebec Network for Research on Protein FunctionStructureand EngineeringQuebec CityQC G1V 0A6Canada Department of Family Medicine Universite´de SherbrookeSherbrookeQC J1H 5N4Canada

Recent proteogenomic approaches have led to the discovery that regions of the transcriptome previously annotated as non-coding regions[i.e.,untranslated regions(UTRs),open reading frames overlapping annotated coding sequences in a different reading frame,and non-coding RNAs]frequently encode proteins,termed alternative proteins(altProts).This suggests that previously identified protein–protein interaction(PPI)networks are partially incomplete because altProts are not present in conventional protein ***,we used the proteogenomic resource OpenProt and a combined spectrum-and peptide-centric analysis for the re-analysis of a highthroughput human network proteomics dataset,thereby revealing the presence of 261 altProts in the *** found 19 genes encoding both an annotated(reference)and an alternative protein interacting with each *** the 117 altProts encoded by pseudogenes,38 are direct interactors of reference proteins encoded by their respective parental ***,we experimentally validate several interactions involving *** data improve the blueprints of the human PPI network and suggest functional roles for hundreds of altProts.

关键词： Alternative protein Protein network Protein–protein interaction Pseudogene Affinity purification mass spectrometry

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Heterologous Expression of Thermolabile Proteins Enhances Thermotolerance in Escherichia coli

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Advances in Microbiology 2016年第9期6卷 602-612页

作者： Yuya Ueda Seiji Yamauchi Shinsuke Fukata Hidetoshi Okuyama Eugene Hayato Morita Rahul Mahadev Shelake Hidenori Hayashi Graduate School of Science and Engineering Ehime University Matsuyama Japan proteo-Science Center Ehime University Matsuyama Japan Laboratory of Environmental Molecular Biology Faculty of Environmental Earth Science Hokkaido University Sapporo Japan Faculty of Agriculture Ehime University Matsuyama Japan Department of Chemistry Faculty of Science Josai University Saitama Japan

Heat shock proteins (HSPs) play important roles in the mechanism of cellular protection against various environmental stresses. It is well known that accumulation of misfolded proteins in a cell triggers the HSPs expression in prokaryotes as well as eukaryotes. In this study, we heterologously expressed two proteins in E. coli, namely, citrate synthase (CpCSY) and malate dehydrogenase (CpMDH) from a psychrophilic bacterium Colwellia psychrerythraea 34H (optimal growth temperature 8°C). Our analyses using circular dichromism along with temperature-dependant enzyme activities measured in purified or direct cell extracts confirmed that the CpCSY and CpMDH are thermolabile and present in misfolded form even at physiological growth temperature. We observed that the cellular levels of HSPs, both GroEL and DnaK cheperonins were increased. Similarly, higher levels were observed for sigma factor s32 which is specific to heat-shock protein expression. These results suggest that the misfolded-thermolabile proteins expressed in E. coli induced the heat shock response. Furthermore, heat treatment (53°C) to wild type E. coli noticeably delayed their growth recovery but cells expressing CpCSY and CpMDH recovered their growth much faster than that of wild type E. coli. This reveals that the HSPs expressed in response to misfolded-thermolabile proteins protected E. coli against heat-induced damage. This novel approach may be a useful tool for investigating stress-tolerance mechanisms of E. coli.

关键词： Heat Shock Proteins σ32 Psychrophilic Proteins Thermotolerance

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Plasmodium vivax Merozoite surface protein 8 is a highly immunogenic protein that localizes to the food vacuole of the malaria parasite

Plasmodium vivax Merozoite surface protein 8 is a highly imm...

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第十一届全国免疫学学术大会

作者： Cheng Yang Wang Bo Sattabongkot Jetsumon Tsuboi Takafumi Han Eun Taek Department of Parasitology Wuxi Medical School Jiangnan University Department of Medical Environmental Biology and Tropical Medicine School of Medicine Kangwon National University Chuncheon Mahidol Vivax Research Unit Faculty of Tropical Medicine Mahidol University Division of Malaria Research Proteo-Science Center Ehime University

Plasmodium vivax merozoite surface protein 8(Pv MSP8)contains GPI motif and double EGF-like domains,which are considered potential targets of protective *** our previous screening,recombinant Pv MSP8(r Pv MSP8)has been highly detected for recognizing with vivax-infected patient ***,the vaccine potential of Pv MSP8 needs adequately *** present study,purified r Pv MSP8 protein possessed potent antigenicity

关键词： Plasmodium vivax malaria MSP8 food vacuole Immunity

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Plasmodium vivax GPI-anchored micronemal antigen(PvGAMA) binds human erythrocytes independent of Duffy antigen status

Plasmodium vivax GPI-anchored micronemal antigen(PvGAMA) bin...

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中国动物学会寄生虫学专业委员会第十届全国寄生虫学青年工作者学术研讨会

作者： Yang Cheng Feng Lu Bo Wang Jian Li Jin-Hee Han Daisuke Ito Deok-Hoon Kong Lubin Jiang Jian Wu Kwon-Soo Ha Eizo Takashima Jetsumon Sattabongkot Won Sun Park Seok-Ho Hong Sanjay A.Desai Louis H.Miller Takafumi Tsuboi Eun-Taek Han Department of Medical Environmental Biology and Tropical Medicine School of MedicineKangwon National University Department of Parasitology Wuxi Medical School Jiangnan University Laboratory of Malaria and Vector Research (LMVR) National Institute of Allergy and Infectious Diseases (NIAID) National Institutes of Health (NIH) Division of Malaria Research Proteo-Science Center Ehime University Department of Molecular and Cellular Biochemistry School of Medicine Kangwon National University Key Laboratory of Molecular Virology & Immunology Unit of Human Parasite Molecular and Cell Biology Institut Pasteur of Shanghai Mahidol Vivax Research Unit Faculty of Tropical Medicine Mahidol University Department of Physiology School of Medicine Kangwon National University Department of Internal Medicine School of Medicine Kangwon National University

Plasmodium vivax, a major agent of malaria in both temperate and tropical climates, has a limited capacity for infecting humans lacking the Duffy(Fy) blood group antigen as this receptor is critical for erythrocyte invasion. Recent surveys in various endemic regions, however, have reported P. vivax infections in Duffy-negative individuals, suggesting that the parasite may utilize alternative receptor-ligand pairs to complete erythrocyte invasion. Here, we identified and characterized a novel parasite ligand, GPI-anchored micronemal antigen(Pv GAMA), that can bind human erythrocytes regardless of Duffy antigen status. Specific antibodies raised against PvG AMA localize the protein to the parasite microneme, consistent with a role in invasion. These antibodies also inhibited Pv GAMA binding to erythrocytes in a dose-dependent manner. Pv GAMA appears to play a role in a sialic acid-independent, chymotrypsin-sensitive invasion pathway. Thus, Pv GAMA may be an adhesion molecule for invasion of Duffy positive and negative human erythrocytes and is an important P. vivax vaccine candidate.

关键词： Plasmodium vivax GAMA erythrocyte binding Duffy negative sialic acid-independent vaccine candidate

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