@article{MTMT:34395421, title = {Truncated titin is structurally integrated into the human dilated cardiomyopathic sarcomere}, url = {https://m2.mtmt.hu/api/publication/34395421}, author = {Kellermayer, Dalma Lucia and Tordai, Hedvig and Kiss, Balázs and Török, György and Péter, Dániel M. and Sayour, Alex Ali and Pólos, Miklós and Hartyánszky, István and Szilveszter, Bálint and Labeit, Siegfried and Gángó, Ambrus and Bedics, Gábor and Bödör, Csaba and Radovits, Tamás and Merkely, Béla Péter and Kellermayer, Miklós}, doi = {10.1172/JCI169753}, journal-iso = {J CLIN INVEST}, journal = {JOURNAL OF CLINICAL INVESTIGATION}, volume = {134}, unique-id = {34395421}, issn = {0021-9738}, year = {2024}, eissn = {1558-8238}, orcid-numbers = {Kellermayer, Dalma Lucia/0000-0003-0398-0801; Tordai, Hedvig/0000-0002-0875-5569; Kiss, Balázs/0000-0002-2347-5928; Török, György/0000-0001-7616-5782; Sayour, Alex Ali/0000-0001-7728-4775; Hartyánszky, István/0000-0003-1909-6500; Szilveszter, Bálint/0000-0003-1530-4288; Labeit, Siegfried/0000-0002-9009-210X; Gángó, Ambrus/0000-0001-9127-5015; Bedics, Gábor/0000-0003-4628-2384; Bödör, Csaba/0000-0002-0729-692X; Merkely, Béla Péter/0000-0001-6514-0723; Kellermayer, Miklós/0000-0002-5553-6553} } @article{MTMT:34267696, title = {Molecular imaging of bacterial outer membrane vesicles based on bacterial surface display}, url = {https://m2.mtmt.hu/api/publication/34267696}, author = {Szöllősi, Dávid and Hajdrik, Polett and Tordai, Hedvig and Horváth, Ildikó and Veres, Dániel and Gillich, Bernadett and Shailaja, Kanni Das and Smeller, László and Bergmann, Ralf Konrad and Bachmann, Michael and Mihály, Judith and Gaál, Anikó and Jezsó, Bálint and Barátki, Balázs Lajos and Kövesdi, Dorottya and Bősze, Szilvia and Szabó, Ildikó and Felföldi, Tamás and Oszwald, Erzsébet and Padmanabhan, Parasuraman and Gulyás, Balázs Zoltán and Hamdani, Nazha and Máthé, Domokos and Varga, Zoltán and Szigeti, Krisztián}, doi = {10.1038/s41598-023-45628-9}, journal-iso = {SCI REP}, journal = {SCIENTIFIC REPORTS}, volume = {13}, unique-id = {34267696}, issn = {2045-2322}, abstract = {The important roles of bacterial outer membrane vesicles (OMVs) in various diseases and their emergence as a promising platform for vaccine development and targeted drug delivery necessitates the development of imaging techniques suitable for quantifying their biodistribution with high precision. To address this requirement, we aimed to develop an OMV specific radiolabeling technique for positron emission tomography (PET). A novel bacterial strain ( E. coli BL21(DE3) ΔnlpI, ΔlpxM ) was created for efficient OMV production, and OMVs were characterized using various methods. SpyCatcher was anchored to the OMV outer membrane using autotransporter-based surface display systems. Synthetic SpyTag-NODAGA conjugates were tested for OMV surface binding and 64 Cu labeling efficiency. The final labeling protocol shows a radiochemical purity of 100% with a ~ 29% radiolabeling efficiency and excellent serum stability. The in vivo biodistribution of OMVs labeled with 64 Cu was determined in mice using PET/MRI imaging which revealed that the biodistribution of radiolabeled OMVs in mice is characteristic of previously reported data with the highest organ uptakes corresponding to the liver and spleen 3, 6, and 12 h following intravenous administration. This novel method can serve as a basis for a general OMV radiolabeling scheme and could be used in vaccine- and drug-carrier development based on bioengineered OMVs.}, year = {2023}, eissn = {2045-2322}, orcid-numbers = {Szöllősi, Dávid/0000-0002-3363-3862; Hajdrik, Polett/0000-0002-5452-4892; Tordai, Hedvig/0000-0002-0875-5569; Veres, Dániel/0000-0002-9687-3556; Smeller, László/0000-0002-3643-3268; Gaál, Anikó/0000-0003-4064-1825; Jezsó, Bálint/0000-0002-1306-4797; Szabó, Ildikó/0000-0002-9844-7841; Felföldi, Tamás/0000-0003-2009-2478; Hamdani, Nazha/0000-0002-3053-0008; Varga, Zoltán/0000-0002-5741-2669} } @article{MTMT:34593465, title = {Nanomechanics combined with HDX reveals allosteric drug binding sites of CFTR NBD1}, url = {https://m2.mtmt.hu/api/publication/34593465}, author = {Padanyi, Rita and Farkas, Bianka and Tordai, Hedvig and Kiss, Balint and Grubmueller, Helmut and Soya, Naoto and Lukacs, Gergely L. and Kellermayer, Miklos and Hegedus, Tamas}, doi = {10.1016/j.csbj.2022.05.036}, journal-iso = {CSBJ}, journal = {COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL}, volume = {20}, unique-id = {34593465}, issn = {2001-0370}, abstract = {Cystic fibrosis (CF) is a frequent genetic disease in Caucasians that is caused by the deletion of F508 (Delta F508) in the nucleotide binding domain 1 (NBD1) of the CF transmembrane conductance regulator (CFTR). The Delta F508 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 Delta F508-CFTR folding and stability defect. Thus, new pharmacophores that would reinstate the wildtype-like conformational stability of the Delta F508-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 hydrogen-deuterium exchange (HDX) experiments. We found that the NBD1 alpha-subdomain with three adjacent strands from the beta-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 alpha-core region and increases the resistance of the Delta F508-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/).}, keywords = {molecular dynamics simulations; CFTR; cystic fibrosis; Hydrogen-deuterium exchange; atomic force spectroscopy; F508 deletion}, year = {2022}, eissn = {2001-0370}, pages = {2587-2599}, orcid-numbers = {Tordai, Hedvig/0000-0002-0875-5569; Soya, Naoto/0000-0003-0086-4389} } @article{MTMT:34593464, title = {Nanomechanics combined with HDX reveals allosteric drug binding sites of CFTR NBD1}, url = {https://m2.mtmt.hu/api/publication/34593464}, author = {Padanyi, Rita and Farkas, Bianka and Tordai, Hedvig and Kiss, Balint and Grubmueller, Helmut and Soya, Naoto and Lukacs, Gergely L. and Kellermayer, Miklos and Hegedus, Tamas}, doi = {10.1016/j.csbj.2022.05.036}, journal-iso = {CSBJ}, journal = {COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL}, volume = {20}, unique-id = {34593464}, issn = {2001-0370}, abstract = {Cystic fibrosis (CF) is a frequent genetic disease in Caucasians that is caused by the deletion of F508 (Delta F508) in the nucleotide binding domain 1 (NBD1) of the CF transmembrane conductance regulator (CFTR). The Delta F508 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 Delta F508-CFTR folding and stability defect. Thus, new pharmacophores that would reinstate the wildtype-like conformational stability of the Delta F508-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 hydrogen-deuterium exchange (HDX) experiments. We found that the NBD1 alpha-subdomain with three adjacent strands from the beta-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 alpha-core region and increases the resistance of the Delta F508-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/).}, keywords = {molecular dynamics simulations; CFTR; cystic fibrosis; Hydrogen-deuterium exchange; atomic force spectroscopy; F508 deletion}, year = {2022}, eissn = {2001-0370}, pages = {2587-2599}, orcid-numbers = {Tordai, Hedvig/0000-0002-0875-5569; Soya, Naoto/0000-0003-0086-4389} } @article{MTMT:33119125, title = {Imaging the Infection Cycle of T7 at the Single Virion Level}, url = {https://m2.mtmt.hu/api/publication/33119125}, author = {Kiss, Bálint and Kiss, Luca Annamária and Lohinai, Zsombor Dávid and Mudra, Dorottya Mária and Tordai, Hedvig and Herényi, Levente and Csik, Gabriella and Kellermayer, Miklós}, doi = {10.3390/ijms231911252}, journal-iso = {INT J MOL SCI}, journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, volume = {23}, unique-id = {33119125}, issn = {1661-6596}, abstract = {T7 phages are E. coli-infecting viruses that find and invade their target with high specificity and efficiency. The exact molecular mechanisms of the T7 infection cycle are yet unclear. As the infection involves mechanical events, single-particle methods are to be employed to alleviate the problems of ensemble averaging. Here we used TIRF microscopy to uncover the spatial dynamics of the target recognition and binding by individual T7 phage particles. In the initial phase, T7 virions bound reversibly to the bacterial membrane via two-dimensional diffusive exploration. Stable bacteriophage anchoring was achieved by tail-fiber complex to receptor binding which could be observed in detail by atomic force microscopy (AFM) under aqueous buffer conditions. The six anchored fibers of a given T7 phage-displayed isotropic spatial orientation. The viral infection led to the onset of an irreversible structural program in the host which occurred in three distinct steps. First, bacterial cell surface roughness, as monitored by AFM, increased progressively. Second, membrane blebs formed on the minute time scale (average ~5 min) as observed by phase-contrast microscopy. Finally, the host cell was lysed in a violent and explosive process that was followed by the quick release and dispersion of the phage progeny. DNA ejection from T7 could be evoked in vitro by photothermal excitation, which revealed that genome release is mechanically controlled to prevent premature delivery of host-lysis genes. The single-particle approach employed here thus provided an unprecedented insight into the details of the complete viral cycle.}, keywords = {AFM; atomic force microscopy (AFM); total internal reflection fluorescence (TIRF); TIRF; bacterial lysis; CC single-particle imaging}, year = {2022}, eissn = {1422-0067}, orcid-numbers = {Kiss, Bálint/0000-0002-1595-0426; Lohinai, Zsombor Dávid/0000-0003-0135-6028; Tordai, Hedvig/0000-0002-0875-5569; Herényi, Levente/0000-0003-0535-0256; Csik, Gabriella/0000-0001-8464-2534; Kellermayer, Miklós/0000-0002-5553-6553} } @article{MTMT:33084278, title = {Comprehensive Collection and Prediction of ABC Transmembrane Protein Structures in the AI Era of Structural Biology}, url = {https://m2.mtmt.hu/api/publication/33084278}, author = {Tordai, Hedvig and Suhajda, Erzébet and Sillitoe, Ian and Nair, Sreenath and Varadi, Mihaly and Hegedűs, Tamás}, doi = {10.3390/ijms23168877}, journal-iso = {INT J MOL SCI}, journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, volume = {23}, unique-id = {33084278}, issn = {1661-6596}, abstract = {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.}, keywords = {MECHANISM; CLASSIFICATION; MUTATIONS; CHANNEL; P-GLYCOPROTEIN; TRANSPORTERS; protein structure; inventory; ABC TRANSPORTERS; PROTEIN COMPLEX; Biochemistry & Molecular Biology; Structure database; AlphaFold2; AF-multimer}, year = {2022}, eissn = {1422-0067}, orcid-numbers = {Tordai, Hedvig/0000-0002-0875-5569; Varadi, Mihaly/0000-0002-3687-0839; Hegedűs, Tamás/0000-0002-0331-9629} } @article{MTMT:32853643, title = {Nanomechanics combined with HDX reveals allosteric drug binding sites of CFTR NBD1}, url = {https://m2.mtmt.hu/api/publication/32853643}, author = {Padányi, Rita and Farkas, Bianka Vivien and Tordai, Hedvig and Kiss, Bálint and Grubmüller, Helmut and Soya, Naoto and Lukács, Gergely L. and Kellermayer, Miklós and Hegedűs, Tamás}, doi = {10.1016/j.csbj.2022.05.036}, journal-iso = {CSBJ}, journal = {COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL}, volume = {20}, unique-id = {32853643}, issn = {2001-0370}, abstract = {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/).}, year = {2022}, eissn = {2001-0370}, pages = {2587-2599}, orcid-numbers = {Padányi, Rita/0000-0001-7798-0463; Farkas, Bianka Vivien/0000-0002-0258-6864; Tordai, Hedvig/0000-0002-0875-5569; Kiss, Bálint/0000-0002-1595-0426; Kellermayer, Miklós/0000-0002-5553-6553; Hegedűs, Tamás/0000-0002-0331-9629} } @article{MTMT:32333761, title = {Increased expression of N2BA titin corresponds to more compliant myofibrils in athlete’s heart}, url = {https://m2.mtmt.hu/api/publication/32333761}, author = {Kellermayer, Dalma Lucia and Kiss, Bálint and Tordai, Hedvig and Oláh, Attila and Granzier, H and Merkely, Béla Péter and Kellermayer, Miklós and Radovits, Tamás}, doi = {10.3390/ijms222011110}, journal-iso = {INT J MOL SCI}, journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, volume = {22}, unique-id = {32333761}, issn = {1661-6596}, year = {2021}, eissn = {1422-0067}, orcid-numbers = {Kellermayer, Dalma Lucia/0000-0003-0398-0801; Kiss, Bálint/0000-0002-1595-0426; Tordai, Hedvig/0000-0002-0875-5569; Merkely, Béla Péter/0000-0001-6514-0723; Kellermayer, Miklós/0000-0002-5553-6553} } @article{MTMT:31859888, title = {Development, structure and mechanics of a synthetic E. coli outer membrane model}, url = {https://m2.mtmt.hu/api/publication/31859888}, author = {Kiss, Bálint and Bozó, Tamás and Mudra, Dorottya Mária and Tordai, Hedvig and Herényi, Levente and Kellermayer, Miklós}, doi = {10.1039/D0NA00977F}, journal-iso = {NANOSCALE ADV}, journal = {NANOSCALE ADVANCES}, volume = {3}, unique-id = {31859888}, issn = {2516-0230}, year = {2021}, eissn = {2516-0230}, pages = {755-766}, orcid-numbers = {Kiss, Bálint/0000-0002-1595-0426; Bozó, Tamás/0000-0002-2643-0661; Mudra, Dorottya Mária/0000-0001-7143-0559; Tordai, Hedvig/0000-0002-0875-5569; Herényi, Levente/0000-0003-0535-0256; Kellermayer, Miklós/0000-0002-5553-6553} } @article{MTMT:31623716, title = {The transport pathway in the ABCG2 protein and its regulation revealed by molecular dynamics simulations}, url = {https://m2.mtmt.hu/api/publication/31623716}, author = {Nagy, Tamás and Tóth, Ágota and Telbisz, Ágnes Mária and Sarkadi, Balázs and Tordai, Hedvig and Tordai, Attila and Hegedűs, Tamás}, doi = {10.1007/s00018-020-03651-3}, journal-iso = {CELL MOL LIFE SCI}, journal = {CELLULAR AND MOLECULAR LIFE SCIENCES}, volume = {78}, unique-id = {31623716}, issn = {1420-682X}, abstract = {Atomic-level structural insight on the human ABCG2 membrane protein, a pharmacologically important transporter, has been recently revealed by several key papers. In spite of the wealth of structural data, the pathway of transmembrane movement for the large variety of structurally different ABCG2 substrates and the physiological lipid regulation of the transporter has not been elucidated. The complex molecular dynamics simulations presented here may provide a breakthrough in understanding the steps of the substrate transport process and its regulation by cholesterol. Our analysis revealed drug binding cavities other than the central binding site and delineated a putative dynamic transport pathway for substrates with variable structures. We found that membrane cholesterol accelerated drug transport by promoting the closure of cytoplasmic protein regions. Since ABCG2 is present in all major biological barriers and drug-metabolizing organs, influences the pharmacokinetics of numerous clinically applied drugs, and plays a key role in uric acid extrusion, this information may significantly promote a reliable prediction of clinically important substrate characteristics and drug-drug interactions. © 2020, The Author(s).}, keywords = {ABCG2; molecular dynamics; cholesterol regulation; Multidrug transport}, year = {2021}, eissn = {1420-9071}, pages = {2329-2339}, orcid-numbers = {Nagy, Tamás/0000-0002-0137-4341; Telbisz, Ágnes Mária/0000-0003-0972-4606; Sarkadi, Balázs/0000-0003-0592-4539; Tordai, Hedvig/0000-0002-0875-5569; Tordai, Attila/0000-0001-6966-1622; Hegedűs, Tamás/0000-0002-0331-9629} }