TY - JOUR AU - Berta, Blanka AU - Tordai, Hedvig AU - Lukács, G.L. AU - Papp, B. AU - Enyedi, Ágnes AU - Padányi, Rita AU - Hegedűs, Tamás TI - SARS-CoV-2 envelope protein alters calcium signaling via SERCA interactions JF - SCIENTIFIC REPORTS J2 - SCI REP VL - 14 PY - 2024 IS - 1 PG - 15 SN - 2045-2322 DO - 10.1038/s41598-024-71144-5 UR - https://m2.mtmt.hu/api/publication/35306993 ID - 35306993 LA - English DB - MTMT ER - TY - JOUR AU - Laczkó-Dobos, Hajnalka AU - Bhattacharjee, Arindam AU - Maddali, Asha Kiran AU - Kincses, András AU - Abuammar, Hussein AU - Sebőkné Nagy, Krisztina AU - Páli, Tibor AU - Dér, András AU - Hegedűs, Tamás AU - Csordás, Gábor AU - Juhász, Gábor TI - PtdIns4p is required for the autophagosomal recruitment of STX17 (syntaxin 17) to promote lysosomal fusion JF - AUTOPHAGY J2 - AUTOPHAGY VL - 20 PY - 2024 IS - 7 SP - 1639 EP - 1650 PG - 12 SN - 1554-8627 DO - 10.1080/15548627.2024.2322493 UR - https://m2.mtmt.hu/api/publication/34724664 ID - 34724664 N1 - Institute of Genetics, HUN-REN Biological Research Centre Szeged, Szeged, Hungary Doctoral School of Biology, University of Szeged, Szeged, Hungary Institute of Biophysics, HUN-REN Biological Research Centre Szeged, Szeged, Hungary Department of Biophysics and Radiation Biology, Semmelweis University, Budapest, Hungary HUN-REN Biophysical Virology Research Group, Budapest, Hungary Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Budapest, Hungary Cited By :3 Export Date: 5 September 2024 Correspondence Address: Juhász, G.; HUN-REN Biological Research Centre Szeged, Temesvari krt. 62, Hungary; email: juhasz.gabor@brc.hu Chemicals/CAS: alanine, 56-41-7, 6898-94-8; arginine, 1119-34-2, 15595-35-4, 7004-12-8, 74-79-3; lipid, 66455-18-3; lysine, 56-87-1, 6899-06-5, 70-54-2; Liposomes; phosphatidylinositol 4-phosphate; Phosphatidylinositol Phosphates; Qa-SNARE Proteins; STX17 protein, human LA - English DB - MTMT ER - TY - JOUR AU - Naffa, R. AU - Hegedűs, L. AU - Hegedűs, Tamás AU - Tóth, Sarolta AU - Papp, B. AU - Tordai, Attila AU - Enyedi, Ágnes TI - Plasma membrane Ca2+ pump isoform 4 function in cell migration and cancer metastasis JF - JOURNAL OF PHYSIOLOGY-LONDON J2 - J PHYSIOL-LONDON VL - 602 PY - 2024 IS - 8 SP - 1551 EP - 1564 PG - 14 SN - 0022-3751 DO - 10.1113/JP284179 UR - https://m2.mtmt.hu/api/publication/33731782 ID - 33731782 N1 - Molecular Biology Research Laboratory, School of Medicine, The University of Jordan, Amman, Jordan Department of Thoracic Surgery, Ruhrlandklinik, University Clinic Essen, Essen, Germany Department of Biophysics and Radiation Biology, Semmelweis University, Budapest, Hungary ELKH-SE Biophysical Virology Research Group, Eötvös Loránd Research Network, Budapest, Hungary Department of Transfusion Medicine, Semmelweis University, Budapest, Hungary Institut National de la Santé et de la Recherche Médicale, Institut de Recherche Saint-Louis, Hôpital Saint-Louis, Paris, France Institut de Recherche Saint-Louis, Hôpital Saint-Louis, Université de Paris, Paris, France CEA, DRF-Institut Francois Jacob, Department of Hemato-Immunology Research, Hôpital Saint-Louis, Paris, France Cited By :1 Export Date: 26 June 2024 CODEN: JPHYA Correspondence Address: Enyedi, Á.; Department of Transfusion Medicine, Hungary; email: enyedi.agnes@med.semmelweis-univ.hu LA - English DB - MTMT ER - TY - JOUR AU - Tordai, Hedvig AU - Torres, O. AU - Csepi, M. AU - Padányi, Rita AU - Lukács, G.L. AU - Hegedűs, Tamás TI - Analysis of AlphaMissense data in different protein groups and structural context JF - SCIENTIFIC DATA J2 - SCI DATA VL - 11 PY - 2024 IS - 1 PG - 9 SN - 2052-4463 DO - 10.1038/s41597-024-03327-8 UR - https://m2.mtmt.hu/api/publication/34879391 ID - 34879391 LA - English DB - MTMT ER - TY - JOUR AU - Vaccarin, Christian AU - Veit, Guido AU - Hegedűs, Tamás AU - Torres Constante, Karen Odalys AU - Chilin, Adriana AU - Lukacs, Gergely L. AU - Marzaro, Giovanni TI - Synthesis and Biological Evaluation of Pyrazole-Pyrimidones as a New Class of Correctors of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) JF - JOURNAL OF MEDICINAL CHEMISTRY J2 - J MED CHEM VL - 67 PY - 2024 IS - 16 SP - 13891 EP - 13908 PG - 18 SN - 0022-2623 DO - 10.1021/acs.jmedchem.4c00685 UR - https://m2.mtmt.hu/api/publication/35182006 ID - 35182006 AB - Cystic fibrosis (CF) is caused by the functional expression defect of the cystic fibrosis transmembrane conductance regulator (CFTR) protein. Despite the recent success in CFTR modulator development, the available correctors only partially restore the F508del-CFTR channel function, and several rare CF mutations show resistance to available drugs. We previously identified compound 4172 that synergistically rescued the F508del-CFTR folding defect in combination with the existing corrector drugs VX-809 and VX-661. Here, novel CFTR correctors were designed by applying a classical medicinal chemistry approach on the 4172 scaffold. Molecular docking and three-dimensional quantitative structure-activity relationship (3D-QSAR) studies were conducted to propose a plausible binding site and design more potent and effective analogs. We identified three optimized compounds, which, in combination with VX-809 and the investigational corrector 3151, increased the plasma membrane density and function of F508del-CFTR and other rare CFTR mutants resistant to the currently approved therapies. LA - English DB - MTMT ER - TY - JOUR AU - Basu, S. AU - Hegedűs, Tamás AU - Kurgan, L. TI - CoMemMoRFPred: Sequence-based Prediction of MemMoRFs by Combining Predictors of Intrinsic Disorder, MoRFs and Disordered Lipid-binding Regions JF - JOURNAL OF MOLECULAR BIOLOGY J2 - J MOL BIOL VL - 435 PY - 2023 IS - 21 PG - 14 SN - 0022-2836 DO - 10.1016/j.jmb.2023.168272 UR - https://m2.mtmt.hu/api/publication/34163279 ID - 34163279 N1 - Export Date: 17 November 2023 CODEN: JMOBA Correspondence Address: Kurgan, L.; Department of Computer Science, 401 West Main Street, Room E4225, United States; email: lkurgan@vcu.edu LA - English DB - MTMT ER - TY - JOUR AU - Mózner, Orsolya AU - Zámbó, Boglárka AU - Bartos, Zsuzsa AU - Gergely, Anna AU - Szabó, Kata Sára AU - Jezsó, Bálint AU - Telbisz, Ágnes Mária AU - Várady, György AU - Homolya, László AU - Hegedűs, Tamás AU - Sarkadi, Balázs TI - Expression, Function and Trafficking of the Human ABCG2 Multidrug Transporter Containing Mutations in an Unstructured Cytoplasmic Loop JF - MEMBRANES (BASEL) J2 - MEMBRANES-BASEL VL - 13 PY - 2023 IS - 10 PG - 14 SN - 2077-0375 DO - 10.3390/membranes13100822 UR - https://m2.mtmt.hu/api/publication/34175360 ID - 34175360 AB - The human ABCG2 multidrug transporter plays a crucial role in the absorption and excretion of xeno- and endobiotics, contributes to cancer drug resistance and the development of gout. In this work, we have analyzed the effects of selected variants, residing in a structurally unresolved cytoplasmic region (a.a. 354–367) of ABCG2 on the function and trafficking of this protein. A cluster of four lysines (K357–360) and the phosphorylation of a threonine (T362) residue in this region have been previously suggested to significantly affect the cellular fate of ABCG2. Here, we report that the naturally occurring K360del variant in human cells increased ABCG2 plasma membrane expression and accelerated cellular trafficking. The variable alanine replacements of the neighboring lysines had no significant effect on transport function, and the apical localization of ABCG2 in polarized cells has not been altered by any of these mutations. Moreover, in contrast to previous reports, we found that the phosphorylation-incompetent T362A, or the phosphorylation-mimicking T362E variants in this loop had no measurable effects on the function or expression of ABCG2. Molecular dynamics simulations indicated an increased mobility of the mutant variants with no major effects on the core structure of the protein. These results may help to decipher the potential role of this unstructured region within this transporter. LA - English DB - MTMT ER - TY - JOUR AU - Singh, Kuljeet AU - Patil, Rajesh B. AU - Patel, Vikas AU - Gálné Remenyik, Judit AU - Hegedűs, Tamás AU - Kormosné, Goda Katalin TI - Synergistic Inhibitory Effect of Quercetin and Cyanidin-3O-Sophoroside on ABCB1 JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 24 PY - 2023 IS - 14 PG - 24 SN - 1661-6596 DO - 10.3390/ijms241411341 UR - https://m2.mtmt.hu/api/publication/34077112 ID - 34077112 AB - The human ABCB1 (P-glycoprotein, Pgp) protein is an active exporter expressed in the plasma membrane of cells forming biological barriers. In accordance with its broad substrate spectrum and tissue expression pattern, it affects the pharmacokinetics of numerous chemotherapeutic drugs and it is involved in unwanted drug–drug interactions leading to side effects or toxicities. When expressed in tumor tissues, it contributes to the development of chemotherapy resistance in malignancies. Therefore, the understanding of the molecular details of the ligand–ABCB1 interactions is of crucial importance. In a previous study, we found that quercetin (QUR) hampers both the transport and ATPase activity of ABCB1, while cyandin-3O-sophroside (C3S) stimulates the ATPase activity and causes only a weak inhibition of substrate transport. In the current study, when QUR and C3S were applied together, both a stronger ATPase inhibition and a robust decrease in substrate transport were observed, supporting their synergistic ABCB1 inhibitory effect. Similar to cyclosporine A, a potent ABCB1 inhibitor, co-treatment with QUR and C3S shifted the conformational equilibrium to the “inward-facing” conformer of ABCB1, as it was detected by the conformation-selective UIC2 mAb. To gain deeper insight into the molecular details of ligand–ABCB1 interactions, molecular docking experiments and MD simulations were also carried out. Our in silico studies support that QUR and C3S can bind simultaneously to ABCB1. The most favourable ligand–ABCB1 interaction is obtained when C3S binds to the central substrate binding site and QUR occupies the “access tunnel”. Our results also highlight that the strong ABCB1 inhibitory effect of the combined treatment with QUR and C3S may be exploited in chemotherapy protocols for the treatment of multidrug-resistant tumors or for improving drug delivery through pharmacological barriers. LA - English DB - MTMT ER - TY - JOUR AU - Soya, N. AU - Xu, H. AU - Roldan, A. AU - Yang, Z. AU - Ye, H. AU - Jiang, F. AU - Premchandar, A. AU - Veit, G. AU - Cole, S.P.C. AU - Kappes, J. AU - Hegedűs, Tamás AU - Lukacs, G.L. TI - Folding correctors can restore CFTR posttranslational folding landscape by allosteric domain–domain coupling JF - NATURE COMMUNICATIONS J2 - NAT COMMUN VL - 14 PY - 2023 IS - 1 PG - 21 SN - 2041-1723 DO - 10.1038/s41467-023-42586-8 UR - https://m2.mtmt.hu/api/publication/34257929 ID - 34257929 LA - English DB - MTMT ER - TY - JOUR AU - Hegedűs, Tamás AU - Geisler, Markus AU - Lukács, Gergely László AU - Farkas, Bianka Vivien TI - Ins and outs of AlphaFold2 transmembrane protein structure predictions JF - CELLULAR AND MOLECULAR LIFE SCIENCES J2 - CELL MOL LIFE SCI VL - 79 PY - 2022 IS - 1 PG - 12 SN - 1420-682X DO - 10.1007/s00018-021-04112-1 UR - https://m2.mtmt.hu/api/publication/32612583 ID - 32612583 LA - English DB - MTMT ER -