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 - AiP PY - 2024 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 Export Date: 27 March 2024 Correspondence Address: Juhász, G.; HUN-REN Biological Research Centre Szeged, Temesvari krt. 62, Hungary; email: juhasz.gabor@brc.hu 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 PY - 2024 SN - 0022-3751 DO - 10.1113/JP284179 UR - https://m2.mtmt.hu/api/publication/33731782 ID - 33731782 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 - TY - JOUR AU - Hegyi, Zoltán AU - Hegedűs, Tamás AU - Homolya, László TI - The Reentry Helix Is Potentially Involved in Cholesterol Sensing of the ABCG1 Transporter Protein JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 23 PY - 2022 IS - 22 PG - 16 SN - 1661-6596 DO - 10.3390/ijms232213744 UR - https://m2.mtmt.hu/api/publication/33293571 ID - 33293571 LA - English DB - MTMT ER - TY - JOUR AU - Padányi, Rita AU - Farkas, Bianka Vivien AU - Tordai, Hedvig AU - Kiss, Bálint AU - Grubmüller, Helmut AU - Soya, Naoto AU - Lukács, Gergely L. AU - Kellermayer, Miklós AU - Hegedűs, Tamás TI - Nanomechanics combined with HDX reveals allosteric drug binding sites of CFTR NBD1 JF - COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL J2 - CSBJ VL - 20 PY - 2022 SP - 2587 EP - 2599 PG - 13 SN - 2001-0370 DO - 10.1016/j.csbj.2022.05.036 UR - https://m2.mtmt.hu/api/publication/32853643 ID - 32853643 AB - Cystic fibrosis (CF) is a frequent genetic disease in Caucasians that is caused by the deletion of F508 (DF508) in the nucleotide binding domain 1 (NBD1) of the CF transmembrane conductance regulator (CFTR). The DF508 compromises the folding energetics of the NBD1, as well as the folding of three other CFTR domains. Combination of FDA approved corrector molecules can efficiently but incompletely rescue the DF508-CFTR folding and stability defect. Thus, new pharmacophores that would reinstate the wildtype-like conformational stability of the DF508-NBD1 would be highly beneficial. The most prominent molecule, 5-bromoindole-3-acetic acid (BIA) that can thermally stabilize the NBD1 has low potency and efficacy. To gain insights into the NBD1 (un)folding dynamics and BIA binding site localization, we combined molecular dynamics (MD) simulations, atomic force spectroscopy (AFM) and hydrogendeuterium exchange (HDX) experiments. We found that the NBD1 a-subdomain with three adjacent strands from the b-subdomain plays an important role in early folding steps, when crucial non-native interactions are formed via residue F508. Our AFM and HDX experiments showed that BIA associates with this a-core region and increases the resistance of the DF508-NBD1 against mechanical unfolding, a phenomenon that could be exploited in future developments of folding correctors. (c) 2022 The Authors. Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). LA - English DB - MTMT ER - TY - JOUR AU - Tordai, Hedvig AU - Suhajda, Erzébet AU - Sillitoe, Ian AU - Nair, Sreenath AU - Varadi, Mihaly AU - Hegedűs, Tamás TI - Comprehensive Collection and Prediction of ABC Transmembrane Protein Structures in the AI Era of Structural Biology JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 23 PY - 2022 IS - 16 PG - 16 SN - 1661-6596 DO - 10.3390/ijms23168877 UR - https://m2.mtmt.hu/api/publication/33084278 ID - 33084278 AB - The number of unique transmembrane (TM) protein structures doubled in the last four years, which can be attributed to the revolution of cryo-electron microscopy. In addition, AlphaFold2 (AF2) also provided a large number of predicted structures with high quality. However, if a specific protein family is the subject of a study, collecting the structures of the family members is highly challenging in spite of existing general and protein domain-specific databases. Here, we demonstrate this and assess the applicability and usability of automatic collection and presentation of protein structures via the ABC protein superfamily. Our pipeline identifies and classifies transmembrane ABC protein structures using the PFAM search and also aims to determine their conformational states based on special geometric measures, conftors. Since the AlphaFold database contains structure predictions only for single polypeptide chains, we performed AF2-Multimer predictions for human ABC half transporters functioning as dimers. Our AF2 predictions warn of possibly ambiguous interpretation of some biochemical data regarding interaction partners and call for further experiments and experimental structure determination. We made our predicted ABC protein structures available through a web application, and we joined the 3D-Beacons Network to reach the broader scientific community through platforms such as PDBe-KB. LA - English DB - MTMT ER -