TY  - JOUR
DA  - 2018/02/01
VL  - 8
IS  - 1
SP  - 2086
AU  - Lopes de Carvalho, Leonor
AU  - Elovaara, Heli
AU  - De Ruyck, Jerome
AU  - Vergoten, Gerard
AU  - Jalkanen, Sirpa
AU  - Guédez, Gabriela
AU  - Salminen, Tiina A.
TI  - Mapping the interaction site and effect of the Siglec-9 inflammatory biomarker on human primary amine oxidase
DO  - 10.1038/s41598-018-20618-4
JA  - Sci Rep
LA  - Anglais
UR  - http://hdl.handle.net/20.500.12210/18293
SN  - 2045-2322
AB  - Human primary amine oxidase (hAOC3), also known as vascular adhesion protein 1, mediates leukocyte rolling and trafficking to sites of inflammation by a multistep adhesion cascade. hAOC3 is absent on the endothelium of normal tissues and is kept upregulated during inflammatory conditions, which is an applicable advantage for imaging inflammatory diseases. Sialic acid binding immunoglobulin like-lectin 9 (Siglec-9) is a leukocyte ligand for hAOC3. The peptide (CARLSLSWRGLTLCPSK) based on the region of Siglec-9 that interacts with hAOC3, can be used as a specific tracer for hAOC3-targeted imaging of inflammation using Positron Emission Tomography (PET). In the present study, we show that the Siglec-9 peptide binds to hAOC3 and triggers its amine oxidase activity towards benzylamine. Furthermore, the hAOC3 inhibitors semicarbazide and imidazole reduce the binding of wild type and Arg/Ala mutated Siglec-9 peptides to hAOC3. Molecular docking of the Siglec-9 peptide is in accordance with the experimental results and predicts that the R3 residue in the peptide interacts in the catalytic site of hAOC3 when the topaquinone cofactor is in the non-catalytic on-copper conformation. The predicted binding mode of Siglec-9 peptide to hAOC3 is supported by the PET studies using rodent, rabbit and pig AOC3 proteins.
KW  - Computational models
KW  - Diagnostic markers
KW  - Glycoproteins
KW  - Inflammation
KW  - peptides
JO  - Scientific Reports
ER  - 
TY  - JOUR
DA  - 2018/12/
VL  - 8
IS  - 1
SP  - 7017
AU  - Tsuchida, Akiko
AU  - Senda, Motohiro
AU  - Ito, Akihiro
AU  - Saito, Seiichi
AU  - Kiso, Makoto
AU  - Ando, Takayuki
AU  - Harduin Lepers, Anne
AU  - Matsuda, Akio
AU  - Furukawa, Keiko
AU  - Furukawa, Koichi
TI  - Roles of GalNAc-disialyl Lactotetraosyl Antigens in Renal Cancer Cells
DO  - 10.1038/s41598-018-25521-6
JA  - Sci Rep
LA  - Anglais
UR  - http://hdl.handle.net/20.500.12210/18632
SN  - 2045-2322
AB  - GalNAc-disialyl Lc4 (GalNAc-DSLc4) was reported as a novel antigen that associated with malignant features of renal cell cancers (RCCs). To clarify roles of GalNAc-DSLc4 in malignant properties of RCCs, we identified B4GalNAc-T2 as a responsible gene for the synthesis of GalNAc-DSLc4, and prepared stable transfectants of GalNAc-T2 cDNA using VMRC-RCW cells, resulting in the establishment of high expressants of GalNAc-DSLc4. They showed increased proliferation and invasion, and specific adhesion to laminin. In the transfectants, PI3K/Akt signals were highly activated by serum stimulation or adhesion to laminin. GalNAc-DSLc4 was co-localized in lipid rafts with integrin β1 and caveolin-1 in both immunoblotting of fractionated detergent extracts and immunocytostaining, particularly when stimulated with serum. Masking of GalNAc-DSLc4 with antibodies as well as PI3K inhibitor suppressed malignant properties of the transfectants. These results suggested that GalNAc-DSLc4 is involved in malignant properties of RCCs by forming a molecular complex with integrins in lipid rafts.
PB  - Nature Research
JO  - Scientific Reports
ER  - 
TY  - JOUR
DA  - 2020/06/18
VL  - 10
IS  - 1
AU  - Dorival, Jonathan
AU  - Philys, Sonia
AU  - Giuntini, Elisa
AU  - Brailly, Romain
AU  - De Ruyck, Jerome
AU  - Czjzek, Mirjam
AU  - Biondi, Emanuele
AU  - Bompard, Coralie
TI  - Structural and enzymatic characterisation of the Type III effector NopAA (=GunA) from Sinorhizobium fredii USDA257 reveals a Xyloglucan hydrolase activity
DO  - 10.1038/s41598-020-67069-4
JA  - Sci Rep
UR  - http://hdl.handle.net/20.500.12210/29577
SN  - 2045-2322
PB  - Springer Science and Business Media LLC
JO  - Scientific Reports
ER  - 
TY  - JOUR
DA  - 2018/12/
VL  - 8
IS  - 1
AU  - Cenci, Ugo
AU  - Qiu, H.
AU  - Pillonel, T.
AU  - Cardol, P.
AU  - Remacle, C.
AU  - Colleoni, Christophe
AU  - Kadouche, Derifa
AU  - Chabi, Malika
AU  - Greub, G.
AU  - Bhattacharya, Debashish
AU  - Ball, Steven
TI  - Host-pathogen biotic interactions shaped vitamin K metabolism in Archaeplastida
DO  - 10.1038/s41598-018-33663-w
LA  - Anglais
UR  - http://hdl.handle.net/20.500.12210/18705
SN  - 2045-2322
AB  - Menaquinone (vitamin K2) shuttles electrons between membrane-bound respiratory complexes under microaerophilic conditions. In photosynthetic eukaryotes and cyanobacteria, phylloquinone (vitamin K1) participates in photosystem I function. Here we elucidate the evolutionary history of vitamin K metabolism in algae and plants. We show that Chlamydiales intracellular pathogens made major genetic contributions to the synthesis of the naphthoyl ring core and the isoprenoid side-chain of these quinones. Production of the core in extremophilic red algae is under control of a menaquinone (Men) gene cluster consisting of 7 genes that putatively originated via lateral gene transfer (LGT) from a chlamydial donor to the plastid genome. In other green and red algae, functionally related nuclear genes also originated via LGT from a non-cyanobacterial, albeit unidentified source. In addition, we show that 3–4 of the 9 required steps for synthesis of the isoprenoid side chains are under control of genes of chlamydial origin. These results are discussed in the light of the hypoxic response experienced by the cyanobacterial endosymbiont when it gained access to the eukaryotic cytosol.
JO  - Scientific Reports
ER  - 
TY  - JOUR
DA  - 2016/07/
VL  - 6
IS  - 1
AU  - Magalhães, Ana
AU  - Rossez, Yannick
AU  - Masselot, Catherine
AU  - Maes, Emmanuel
AU  - Gomes, Joana
AU  - Shevtsova, Anna
AU  - Bugaytsova, Jeanna
AU  - Borén, Thomas
AU  - Reis, Celso A.
TI  - Muc5ac gastric mucin glycosylation is shaped by FUT2 activity and functionally impacts Helicobacter pylori binding
DO  - 10.1038/srep25575
LA  - Anglais
UR  - http://hdl.handle.net/20.500.12210/18518
SN  - 2045-2322
AB  - The gastrointestinal tract is lined by a thick and complex layer of mucus that protects the mucosal epithelium from biochemical and mechanical aggressions. This mucus barrier confers protection against pathogens but also serves as a binding site that supports a sheltered niche of microbial adherence. The carcinogenic bacteria Helicobacter pylori colonize the stomach through binding to host glycans present in the glycocalyx of epithelial cells and extracellular mucus. The secreted MUC5AC mucin is the main component of the gastric mucus layer, and BabA-mediated binding of H. pylori to MUC5AC confers increased risk for overt disease. In this study we unraveled the O-glycosylation profile of Muc5ac from glycoengineered mice models lacking the FUT2 enzyme and therefore mimicking a non-secretor human phenotype. Our results demonstrated that the FUT2 determines the O-glycosylation pattern of Muc5ac, with Fut2 knock-out leading to a marked decrease in α1,2-fucosylated structures and increased expression of the terminal type 1 glycan structure Lewis-a. Importantly, for the first time, we structurally validated the expression of Lewis-a in murine gastric mucosa. Finally, we demonstrated that loss of mucin FUT2-mediated fucosylation impairs gastric mucosal binding of H. pylori BabA adhesin, which is a recognized feature of pathogenicity.
JO  - Scientific Reports
ER  - 
TY  - JOUR
DA  - 2018/12/
VL  - 8
IS  - 1
AU  - Petit, Daniel
AU  - Teppa, Elin
AU  - Cenci, Ugo
AU  - Ball, Steven
AU  - Harduin Lepers, Anne
TI  - Reconstruction of the sialylation pathway in the ancestor of eukaryotes
DO  - 10.1038/s41598-018-20920-1
LA  - Anglais
UR  - http://hdl.handle.net/20.500.12210/18545
SN  - 2045-2322
AB  - The biosynthesis of sialylated molecules of crucial relevance for eukaryotic cell life is achieved by sialyltransferases (ST) of the CAZy family GT29. These enzymes are widespread in the Deuterostoma lineages and more rarely described in Protostoma, Viridiplantae and various protist lineages raising the question of their presence in the Last eukaryotes Common Ancestor (LECA). If so, it is expected that the main enzymes associated with sialic acids metabolism are also present in protists. We conducted phylogenomic and protein sequence analyses to gain insights into the origin and ancient evolution of ST and sialic acid pathway in eukaryotes, Bacteria and Archaea. Our study uncovered the unreported occurrence of bacterial GT29 ST and evidenced the existence of 2 ST groups in the LECA, likely originating from the endosymbiotic event that generated mitochondria. Furthermore, distribution of the major actors of the sialic acid pathway in the different eukaryotic phyla indicated that these were already present in the LECA, which could also access to this essential monosaccharide either endogenously or via a sialin/sialidase uptake mechanism involving vesicles. This pathway was lost in several basal eukaryotic lineages including Archaeplastida despite the presence of two different ST groups likely assigned to other functions.
JO  - Scientific Reports
ER  - 
TY  - JOUR
DA  - 2016/12/01
VL  - 6
SP  - 38259
AU  - Copie, Guillaume
AU  - Cleri, Fabrizio
AU  - Blossey, Ralf
AU  - Lensink, Marc
TI  - On the ability of molecular dynamics simulation and continuum electrostatics to treat interfacial water molecules in protein-protein complexes
DO  - 10.1038/srep38259
JA  - Sci Rep
LA  - Anglais
UR  - http://hdl.handle.net/20.500.12210/18280
SN  - 2045-2322
AB  - Interfacial waters are increasingly appreciated as playing a key role in protein-protein interactions. We report on a study of the prediction of interfacial water positions by both Molecular Dynamics and explicit solvent-continuum electrostatics based on the Dipolar Poisson-Boltzmann Langevin (DPBL) model, for three test cases: (i) the barnase/barstar complex (ii) the complex between the DNase domain of colicin E2 and its cognate Im2 immunity protein and (iii) the highly unusual anti-freeze protein Maxi which contains a large number of waters in its interior. We characterize the waters at the interface and in the core of the Maxi protein by the statistics of correctly predicted positions with respect to crystallographic water positions in the PDB files as well as the dynamic measures of diffusion constants and position lifetimes. Our approach provides a methodology for the evaluation of predicted interfacial water positions through an investigation of water-mediated inter-chain contacts. While our results show satisfactory behaviour for molecular dynamics simulation, they also highlight the need for improvement of continuum methods.
JO  - Scientific Reports
ER  - 
TY  - JOUR
DA  - 2016/04/
VL  - 6
IS  - 1
AU  - bontemps-gallo, sébastien
AU  - Madec, Edwige
AU  - Masselot, Catherine
AU  - Souche, Erika
AU  - Dondeyne, Jacqueline
AU  - Lacroix, Jean-Marie
TI  - The opgC gene is required for OPGs succinylation and is osmoregulated through RcsCDB and EnvZ/OmpR in the phytopathogen Dickeya dadantii
DO  - 10.1038/srep19619
LA  - Anglais
UR  - http://hdl.handle.net/20.500.12210/18536
SN  - 2045-2322
AB  - Osmoregulated periplasmic glucans (OPGs) are a family of periplasmic oligosaccharides found in the envelope of most Proteobacteria. They are required for virulence of zoo- and phyto-pathogens. The glucose backbone of OPGs is substituted by various kinds of molecules depending on the species, O-succinyl residues being the most widely distributed. In our model, Dickeya dadantii, a phytopathogenic bacteria causing soft rot disease in a wide range of plant species, the backbone of OPGs is substituted by O-succinyl residues in media of high osmolarity and by O-acetyl residues whatever the osmolarity. The opgC gene encoding a transmembrane protein required for the succinylation of the OPGs in D. dadantii was found after an in silico search of a gene encoding a protein with the main characteristics recovered in the two previously characterized OpgC of E. coli and R. sphaeroides, i.e. 10 transmembrane segments and one acyl-transferase domain. Characterization of the opgC gene revealed that high osmolarity expression of the succinyl transferase is controlled by both the EnvZ-OmpR and RcsCDB phosphorelay systems. The loss of O-succinyl residue did not affect the virulence of D. dadantii, suggesting that only the glucose backbone of OPGs is required for virulence.
JO  - Scientific Reports
ER  - 
