TY  - JOUR
AU  - Kellermayer, Dalma Lucia
AU  - Tordai, Hedvig
AU  - Kiss, Balázs
AU  - Török, György
AU  - Péter, Dániel M.
AU  - Sayour, Alex Ali
AU  - Pólos, Miklós
AU  - Hartyánszky, István
AU  - Szilveszter, Bálint
AU  - Labeit, Siegfried
AU  - Gángó, Ambrus
AU  - Bedics, Gábor
AU  - Bödör, Csaba
AU  - Radovits, Tamás
AU  - Merkely, Béla Péter
AU  - Kellermayer, Miklós
TI  - Truncated titin is structurally integrated into the human dilated cardiomyopathic sarcomere
JF  - JOURNAL OF CLINICAL INVESTIGATION
J2  - J CLIN INVEST
VL  - 134
PY  - 2024
IS  - 2
PG  - 13
SN  - 0021-9738
DO  - 10.1172/JCI169753
UR  - https://m2.mtmt.hu/api/publication/34395421
ID  - 34395421
LA  - English
DB  - MTMT
ER  - 

TY  - JOUR
AU  - Szöllősi, Dávid
AU  - Hajdrik, Polett
AU  - Tordai, Hedvig
AU  - Horváth, Ildikó
AU  - Veres, Dániel
AU  - Gillich, Bernadett
AU  - Shailaja, Kanni Das
AU  - Smeller, László
AU  - Bergmann, Ralf Konrad
AU  - Bachmann, Michael
AU  - Mihály, Judith
AU  - Gaál, Anikó
AU  - Jezsó, Bálint
AU  - Barátki, Balázs Lajos
AU  - Kövesdi, Dorottya
AU  - Bősze, Szilvia
AU  - Szabó, Ildikó
AU  - Felföldi, Tamás
AU  - Oszwald, Erzsébet
AU  - Padmanabhan, Parasuraman
AU  - Gulyás, Balázs Zoltán
AU  - Hamdani, Nazha
AU  - Máthé, Domokos
AU  - Varga, Zoltán
AU  - Szigeti, Krisztián
TI  - Molecular imaging of bacterial outer membrane vesicles based on bacterial surface display
JF  - SCIENTIFIC REPORTS
J2  - SCI REP
VL  - 13
PY  - 2023
IS  - 1
PG  - 14
SN  - 2045-2322
DO  - 10.1038/s41598-023-45628-9
UR  - https://m2.mtmt.hu/api/publication/34267696
ID  - 34267696
N1  - Department of Biophysics and Radiation Biology, Semmelweis University, 37-47 Tűzoltó Street, Budapest, 1094, Hungary            
            Institute for Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, 400 Bautzner Landstraße, Dresden, 01328, Germany            
            Biological Nanochemistry Research Group, Institute of Materials and Environmental Chemistry, Research Centre for Natural Sciences, 2 Magyar Tudósok Körútja, Budapest, 1117, Hungary            
            Doctoral School of Biology and Institute of Biology, Eötvös Loránd University, 1/C Pázmány Péter Sétány, Budapest, 1117, Hungary            
            Department of Immunology, ELTE Eötvös Loránd University, 1/C Pázmány Péter Sétány, Budapest, 1117, Hungary            
            MTA-ELTE Complement Research Group, Eötvös Loránd Research Network (ELKH), 1/A Pázmány Péter Sétány, Budapest, 1117, Hungary            
            ELKH-ELTE Research Group of Peptide Chemistry, Eötvös L. Research Network, Eötvös L. University, 1/A Pázmány Péter Sétány, Budapest, 1117, Hungary            
            Department of Microbiology, ELTE Eötvös Loránd University, 1/C Pázmány Péter Sétány, Budapest, 1117, Hungary            
            Centre for Ecological Research, Institute of Aquatic Ecology, 29 Karolina Road, Budapest, 1113, Hungary            
            Department of Anatomy, Histology, and Embryology, Semmelweis University, 58 Tűzoltó Street, Budapest, 1094, Hungary            
            Lee Kong Chian School of Medicine, Nanyang Technological University, 11 Mandalay Road, Singapore, 30823, Singapore            
            Cognitive Neuroimaging Centre, Nanyang Technological University, 59 Nanyang Drive, Singapore, 636921, Singapore            
            Department of Cellular and Translational Physiology, Institute of Physiology, Ruhr University Bochum, Bochum, 44801, Germany            
            HCEMM-Cardiovascular Research Group, Department of Pharmacology and Pharmacotherapy, University of Budapest, Budapest, 1089, Hungary            
            CROmed Translational Research Centers, 37-47 Tűzoltó Street, Budapest, 1094, Hungary            
            In Vivo Imaging Advanced Core Facility, Hungarian Center of Excellence for Molecular Medicine (HCEMM), 37-47 Tűzoltó Street, Budapest, 1094, Hungary            
            Export Date: 30 January 2024            
            Correspondence Address: Szigeti, K.; Department of Biophysics and Radiation Biology, 37-47 Tűzoltó Street, Hungary; email: krisztian.szigeti@gmail.com            
            Funding details: Horizon 2020 Framework Programme, H2020, 739593            
            Funding details: European Commission, EC, 859890            
            Funding details: Magyar Tudományos Akadémia, MTA            
            Funding details: Nemzeti Kutatási Fejlesztési és Innovációs Hivatal, NKFI, 2020.1.16-Jövő-2021–00013, 2020–1.1.2-PIACI-KFI-2020–00021, TKP2021-EGA-31            
            Funding details: Nemzeti Kutatási, Fejlesztési és Innovaciós Alap, NKFIA, EFOP-1.8.0-VEKOP-17-2017-00001            
            Funding details: Innovációs és Technológiai Minisztérium            
            Funding text 1: The authors thank Miklós Geiszt for his contributions to the in vivo experiments, Mihály Kálmán and Ferenc Kilin for their help with the TEM measurements, Wouter Jong and Bart van den Berg van Saparoea for the pHbpD(Δd1) plasmid.            
            Funding text 2: Open access funding provided by Semmelweis University. Zoltán Varga was supported by the János Bolyai Research Scholarship of the Hungarian Academy of Sciences, the ÚNKP-21-5 Bolyai + New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research, Development and Innovation Fund. Ildikó Szabó and Szilvia Bősze thank for the support of grant EFOP-1.8.0-VEKOP-17-2017-00001 and for the ELTE Thematic Excellence Programme the 2018-1.2.1-NKP-2018-00005 project (under the 2018-1.2.1-NKP funding scheme) provided by the Hungarian Ministry for Innovation and Technology, Hungary. Kanni Das Shailaja received support from the European Union under project H2020-SmartAge grant Nr. 859890. This work was supported by The European Union’s Horizon 2020 Research And Innovation Program, grant agreement No 739593: HCEMM, supported by EU Programme: H2020-EU.4.a. This work was also partly funded by grants from the Hungarian National Research, Development and Innovation Office (Thematic Excellence Program, TKP-BIOImaging, financed under the 2020–4.1.1-TKP2020 funding scheme, Investment to the Future 2020.1.16-Jövő-2021–00013, TKP2021-EGA-31 and 2020–1.1.2-PIACI-KFI-2020–00021).
AB  - 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.
LA  - English
DB  - MTMT
ER  - 

TY  - JOUR
AU  - Padanyi, Rita
AU  - Farkas, Bianka
AU  - Tordai, Hedvig
AU  - Kiss, Balint
AU  - Grubmueller, Helmut
AU  - Soya, Naoto
AU  - Lukacs, Gergely L.
AU  - Kellermayer, Miklos
AU  - Hegedus, Tamas
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/34593465
ID  - 34593465
AB  - 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/).
LA  - English
DB  - MTMT
ER  - 

TY  - JOUR
AU  - Padanyi, Rita
AU  - Farkas, Bianka
AU  - Tordai, Hedvig
AU  - Kiss, Balint
AU  - Grubmueller, Helmut
AU  - Soya, Naoto
AU  - Lukacs, Gergely L.
AU  - Kellermayer, Miklos
AU  - Hegedus, Tamas
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/34593464
ID  - 34593464
AB  - 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/).
LA  - English
DB  - MTMT
ER  - 

TY  - JOUR
AU  - Kiss, Bálint
AU  - Kiss, Luca Annamária
AU  - Lohinai, Zsombor Dávid
AU  - Mudra, Dorottya Mária
AU  - Tordai, Hedvig
AU  - Herényi, Levente
AU  - Csik, Gabriella
AU  - Kellermayer, Miklós
TI  - Imaging the Infection Cycle of T7 at the Single Virion Level
JF  - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
J2  - INT J MOL SCI
VL  - 23
PY  - 2022
IS  - 19
PG  - 13
SN  - 1661-6596
DO  - 10.3390/ijms231911252
UR  - https://m2.mtmt.hu/api/publication/33119125
ID  - 33119125
AB  - 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.
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  - 

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  - Kellermayer, Dalma Lucia
AU  - Kiss, Bálint
AU  - Tordai, Hedvig
AU  - Oláh, Attila
AU  - Granzier, H
AU  - Merkely, Béla Péter
AU  - Kellermayer, Miklós
AU  - Radovits, Tamás
TI  - Increased expression of N2BA titin corresponds to more compliant myofibrils in athlete’s heart
JF  - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
J2  - INT J MOL SCI
VL  - 22
PY  - 2021
IS  - 20
PG  - 12
SN  - 1661-6596
DO  - 10.3390/ijms222011110
UR  - https://m2.mtmt.hu/api/publication/32333761
ID  - 32333761
N1  - Funding Agency and Grant Number: New National Excellence Program of The Ministry for Innovation and Technology [UNKP-19-3-I, UNKP-21-3-II-SE-36]; Hungarian National Research, Development and Innovation Office [K135360, K135076]; National Heart Program [NVKP_16-12016-0017]; National Research, Development and Innovation Fund of Hungary [NVKP_16]; Thematic Excellence Programme of the Ministry for Innovation and Technology in Hungary [2020-4.1.1.-TKP2020]; Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences [BO/00837/21]
            Funding text: This research was funded by the UNKP-19-3-I New National Excellence Program of The Ministry for Innovation and Technology to D.K. and grants from the Hungarian National Research, Development and Innovation Office (K135360 to M.K. and K135076 to B.M.). Project no. NVKP_16-12016-0017 (National Heart Program) has been implemented with the support provided by the National Research, Development and Innovation Fund of Hungary, financed under the NVKP_16 funding scheme. The research was financed by the Thematic Excellence Programme (2020-4.1.1.-TKP2020) of the Ministry for Innovation and Technology in Hungary, within the framework of the Therapeutic Development and Bioimaging thematic programs of the Semmelweis University. B.K. was supported by the New National Excellence Program of The Ministry for Innovation and Technology (UNKP-21-3-II-SE-36) and A.O. was supported by the Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences (BO/00837/21).
LA  - English
DB  - MTMT
ER  - 

TY  - JOUR
AU  - Kiss, Bálint
AU  - Bozó, Tamás
AU  - Mudra, Dorottya Mária
AU  - Tordai, Hedvig
AU  - Herényi, Levente
AU  - Kellermayer, Miklós
TI  - Development, structure and mechanics of a synthetic E. coli outer membrane model
JF  - NANOSCALE ADVANCES
J2  - NANOSCALE ADV
VL  - 3
PY  - 2021
IS  - 3
SP  - 755
EP  - 766
PG  - 12
SN  - 2516-0230
DO  - 10.1039/D0NA00977F
UR  - https://m2.mtmt.hu/api/publication/31859888
ID  - 31859888
LA  - English
DB  - MTMT
ER  - 

TY  - JOUR
AU  - Nagy, Tamás
AU  - Tóth, Ágota
AU  - Telbisz, Ágnes Mária
AU  - Sarkadi, Balázs
AU  - Tordai, Hedvig
AU  - Tordai, Attila
AU  - Hegedűs, Tamás
TI  - The transport pathway in the ABCG2 protein and its regulation revealed by molecular dynamics simulations
JF  - CELLULAR AND MOLECULAR LIFE SCIENCES
J2  - CELL MOL LIFE SCI
VL  - 78
PY  - 2021
IS  - 5
SP  - 2329
EP  - 2339
PG  - 11
SN  - 1420-682X
DO  - 10.1007/s00018-020-03651-3
UR  - https://m2.mtmt.hu/api/publication/31623716
ID  - 31623716
AB  - 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).
LA  - English
DB  - MTMT
ER  -