TY - JOUR AU - Gáspárné Csizmadia, Georgina AU - Farkas, Bianka Vivien AU - Katona, E. AU - Tusnády, Gábor AU - Hegedűs, Tamás TI - Using MemBlob to Analyze Transmembrane Regions Based on Cryo-EM Maps JF - METHODS IN MOLECULAR BIOLOGY J2 - METHODS MOL BIOL VL - 2112 PY - 2020 SP - 123 EP - 130 PG - 8 SN - 1064-3745 DO - 10.1007/978-1-0716-0270-6_9 UR - https://m2.mtmt.hu/api/publication/31177534 ID - 31177534 AB - Transmembrane proteins include membrane channels, pores, and receptors and, as such, comprise an important part of the proteome, yet our knowledge about them is much less complete than about soluble, globular proteins. An important aspect of transmembrane protein structure is their exact position within the lipid bilayer, a feature hard to investigate experimentally at the atomic level. Here we describe MemBlob, a novel approach utilizing difference electron density maps obtained by cryo-EM studies of transmembrane proteins. The idea behind is that the nonprotein part of such maps carries information on the exact localization of the membrane mimetics used in the experiment and can be used to extract the positional information of the protein within the membrane. MemBlob uses a structural model of the protein and an experimental electron density map to provide an estimation of the surface residues interacting with the membrane. LA - English DB - MTMT ER - TY - JOUR AU - Farkas, Bianka Vivien AU - Gáspárné Csizmadia, Georgina AU - Katona, Eszter AU - Tusnády, Gábor AU - Hegedűs, Tamás TI - MemBlob database and server for identifying transmembrane regions using cryo-EM maps JF - BIOINFORMATICS J2 - BIOINFORMATICS VL - 36 PY - 2020 IS - 8 SP - 2595 EP - 2598 PG - 4 SN - 1367-4803 DO - 10.1093/bioinformatics/btz539 UR - https://m2.mtmt.hu/api/publication/30745372 ID - 30745372 N1 - Cited By :2 Export Date: 15 May 2020 Department of Biophysics and Radiation Biology, Semmelweis University, Budapest, 1094, Hungary MTA-SE Molecular Biophysics Research Group, Hungarian Academy of Sciences, Budapest, 1094, Hungary Faculty of Information Technology and Bionics, Pázmány Péter Catholic University, Budapest, 1083, Hungary Faculty of Brain Sciences, University College London, London, W1T 7NF, United Kingdom 'Momentum' Membrane Protein Bioinformatics Research Group, Institute of Enzymology, RCNS, Hungarian Academy of Sciences, Budapest, 1117, Hungary Cited By :2 Export Date: 24 July 2020 CODEN: BOINF Correspondence Address: Hegedus, T.; Department of Biophysics and Radiation Biology, Semmelweis UniversityHungary; email: tamas.hegedus@hegelab.org Funding details: HEGEDU18I0 Funding details: K127961, K125607, K119287, K111678 Funding details: Cystic Fibrosis Foundation Funding text 1: This work was supported by the National Research, Development and Innovation Office [K111678, K119287, K125607, K127961], the Cystic Fibrosis Foundation [CFF HEGEDU18I0] and the Semmelweis Science and Innovation Fund. AB - The identification of transmembrane helices in transmembrane proteins is crucial, not only to understand their mechanism of action, but also to develop new therapies. While experimental data on the boundaries of membrane-embedded regions is sparse, this information is present in cryo-electron microscopy (cryo-EM) density maps and it has not been utilized yet for determining membrane regions. We developed a computational pipeline, where the inputs of a cryo-EM map, the corresponding atomistic structure, and the potential bilayer orientation determined by TMDET algorithm of a given protein result in an output defining the residues assigned to the bulk water phase, lipid interface, and the lipid hydrophobic core. Based on this method, we built a database involving published cryo-EM protein structures and a server to be able to compute this data for newly obtained structures.http://memblob.hegelab.org.Supplementary data are available at Bioinformatics online. LA - English DB - MTMT ER - TY - JOUR AU - Farkas, Bianka Vivien AU - Tordai, Hedvig AU - Padányi, Rita AU - Tordai, Attila AU - Gera, János AU - Paragi, Gábor AU - Hegedűs, Tamás TI - Discovering the chloride pathway in the CFTR channel JF - CELLULAR AND MOLECULAR LIFE SCIENCES J2 - CELL MOL LIFE SCI VL - 77 PY - 2020 IS - 4 SP - 765 EP - 778 PG - 12 SN - 1420-682X DO - 10.1007/s00018-019-03211-4 UR - https://m2.mtmt.hu/api/publication/30745347 ID - 30745347 N1 - Funding Agency and Grant Number: Semmelweis Egyetem [Sci_Innov18] Funding Source: Medline; Cystic Fibrosis Foundation (US) [HEGEDU18I0] Funding Source: Medline; Nemzeti Kutatasi, Fejlesztesi es Innovacios Hivatal (HU) [K127961, K111678] Funding Source: Medline Cited By :2 Export Date: 31 August 2021 CODEN: CMLSF Correspondence Address: Hegedűs, T.; Department of Biophysics and Radiation Biology, Hungary; email: hegedus@hegelab.org LA - English DB - MTMT ER - TY - JOUR AU - Mózner, Orsolya AU - Bartos, Zsuzsa AU - Zámbó, Boglárka AU - Homolya, László AU - Hegedűs, Tamás AU - Sarkadi, Balázs TI - Cellular Processing of the ABCG2 Transporter-Potential Effects on Gout and Drug Metabolism. JF - CELLS J2 - CELLS-BASEL VL - 8 PY - 2019 IS - 10 PG - 15 SN - 2073-4409 DO - 10.3390/cells8101215 UR - https://m2.mtmt.hu/api/publication/30924895 ID - 30924895 N1 - Funding Agency and Grant Number: National Research, Development, and Innovation Office [NKFI-127961]; OTKA/NKFIHOrszagos Tudomanyos Kutatasi Alapprogramok (OTKA) [K 128123, NK 115375, FIEK_16-1-2016-0005]; Hungarian Ministry for Innovation and Technology [UNKP-19-3-I-SE-15, UNKP-19-2-I-BME-380] Funding text: This research was funded by National Research, Development, and Innovation Office, grant number NKFI-127961, (T.H.) OTKA/NKFIH grant_K 128123 (L.H.), OTKA/NKFIH grant NK 115375 (B.S.) and FIEK_16-1-2016-0005 (B.S. and L.H.). Z.B. and O.M. were supported by grants UNKP-19-3-I-SE-15 (Z.B.) and UNKP-19-2-I-BME-380 (O.M.) from the Hungarian Ministry for Innovation and Technology. AB - The human ABCG2 is an important plasma membrane multidrug transporter, involved in uric acid secretion, modulation of absorption of drugs, and in drug resistance of cancer cells. Variants of the ABCG2 transporter, affecting cellular processing and trafficking, have been shown to cause gout and increased drug toxicity. In this paper, we overview the key cellular pathways involved in the processing and trafficking of large membrane proteins, focusing on ABC transporters. We discuss the information available for disease-causing polymorphic variants and selected mutations of ABCG2, causing increased degradation and impaired travelling of the transporter to the plasma membrane. In addition, we provide a detailed in silico analysis of an as yet unrecognized loop region of the ABCG2 protein, in which a recently discovered mutation may actually promote ABCG2 membrane expression. We suggest that post-translational modifications in this unstructured loop at the cytoplasmic surface of the protein may have special influence on ABCG2 processing and trafficking. LA - English DB - MTMT ER - TY - CONF AU - Gáspárné Csizmadia, Georgina AU - Farkas, Bianka AU - Katona, Eszter AU - Tusnády, Gábor E. AU - Hegedűs, Tamás TI - Defining Membrane Boundaries of Proteins Using Electron Density Maps: The MemBlob Database and Server T2 - Mechanisms of Membrane Transport Gordon Research Conference PY - 2019 SP - 5 UR - https://m2.mtmt.hu/api/publication/30733928 ID - 30733928 LA - English DB - MTMT ER - TY - CONF AU - Gáspárné Csizmadia, Georgina AU - Farkas, Bianka AU - Katona, Eszter AU - Tusnády, Gábor E. AU - Hegedűs, Tamás TI - USING CRYO-EM MAPS TO DETERMINE PROTEIN TRANSMEMBRANE REGIONS T2 - PhD Tudományos Napok 2019. Előadáskivonatok PB - Semmelweis Egyetem C1 - Budapest PY - 2019 SP - 1 UR - https://m2.mtmt.hu/api/publication/30681403 ID - 30681403 LA - English DB - MTMT ER - TY - BOOK AU - Nagyné Naszályi, Lívia AU - Rein, Verbeke AU - Heleen, Dewitte AU - Fehér, Krisztina AU - Stefaan, De Smedt AU - José, Martins TI - Ceramic core@shell nanospheres as vaccine carriers PY - 2018 UR - https://m2.mtmt.hu/api/publication/30452624 ID - 30452624 AB - The need for new vaccines is evident, but avoiding side effects is crucial for patient compliance. To achieve this, new generation vaccines are being developed. They combine an antigen as a target with the inclusion of an immunostimulant to ensure the induction of immunity, rather than tolerance. Nanoparticles (NPs) are also used as vaccine-delivery systems. With appropriate size and well-chosen injection they are prone to accumulate in immune cells. However, their successful integration into nanovaccines requires thorough analysis of the inorganic/organic interface. I aimed at the elaboration of new vaccine carrier nanosystems, characterized them first by routinely used analytical methods and then by the recently developed solution state NMR spectroscopy toolbox developed at Ghent University [1]. The synthesis of silica@zirconia core@shell nanoparticles was based on Stöber et al. and Kim and coworkers’ method [2, 3]. I decorated the surface of these ceramic NPs with model biomolecules and immune stimulators. The physico-chemical characterization of the particles was carried out using transmission electron microscopy, dynamic light scattering, zeta potential measurements, UV-visible and Fourier-transform infrared spectroscopies. The surface ligand structure was studied by NMR toolbox. Preliminary experiments on biological fate of the as-prepared NPs were carried out (blood stability tests, cell viability assays etc). LA - English DB - MTMT ER - TY - JOUR AU - Zrínyi, Miklós AU - Nakano, Masami TI - Irány a kolloid motor. A kolloidika tudományának egy lehetséges mérnöki alkalmazása JF - MAGYAR KÉMIAI FOLYÓIRAT - KÉMIAI KÖZLEMÉNYEK (1997-) J2 - MAGY KÉM FOLY KÉM KÖZL VL - 124 PY - 2018 IS - 4 SP - 183 EP - 188 PG - 6 SN - 1418-9933 DO - 10.24100/MKF.2018.04.183 UR - https://m2.mtmt.hu/api/publication/30421872 ID - 30421872 LA - Hungarian DB - MTMT ER - TY - JOUR AU - Gáspárné Csizmadia, Georgina AU - Farkas, Bianka Vivien AU - Spagina, Zoltán AU - Tordai, Hedvig AU - Hegedűs, Tamás TI - Quantitative comparison of ABC membrane protein type I exporter structures in a standardized way JF - COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL J2 - CSBJ VL - 16 PY - 2018 SP - 396 EP - 403 PG - 8 SN - 2001-0370 DO - 10.1016/j.csbj.2018.10.008 UR - https://m2.mtmt.hu/api/publication/30336891 ID - 30336891 N1 - MTA-SE Molecular Biophysics Research Group, Hungarian Academy of Sciences, Budapest, Hungary Department of Biophysics and Radiation Biology, Semmelweis University, Budapest, Hungary Faculty of Information Technology, Pázmány Péter Catholic University, Budapest, Hungary Cited By :2 Export Date: 11 August 2021 Correspondence Address: Hegedűs, T.; MTA-SE Molecular Biophysics Research Group, Hungary; email: hegedus@hegelab.org Funding Agency and Grant Number: National Research, Development and Innovation Ofice, Hungary [NKFIH K 111678]; Cystic Fibrosis Foundation, USA [HEGEDU18I0]; NIIF National Information Infrastructure Development Institute; MTA Wigner GPU Laboratory Funding text: This work was supported by National Research, Development and Innovation Ofice, Hungary (NKFIH K 111678) and Cystic Fibrosis Foundation, USA(HEGEDU18I0). We acknowledge NIIF National Information Infrastructure Development Institute (http://www.niif.hu/en), and MTA Wigner GPU Laboratory (http://gpu.wigner.mta.hu) for awarding us access to resources based in Hungary, and the support of their stuff is gratefully acknowledged. Donation of a Quadro P6000 GPU by NVIDIA Corporation is greatly appreciated. MTA-SE Molecular Biophysics Research Group, Hungarian Academy of Sciences, Budapest, Hungary Department of Biophysics and Radiation Biology, Semmelweis University, Budapest, Hungary Faculty of Information Technology, Pázmány Péter Catholic University, Budapest, Hungary Cited By :2 Export Date: 31 August 2021 Correspondence Address: Hegedűs, T.; MTA-SE Molecular Biophysics Research Group, Hungary; email: hegedus@hegelab.org AB - An increasing number of ABC membrane protein structures are determined by cryo-electron microscopy and X-ray crystallography, consequently identifying differences between their conformations has become an arising issue. Therefore, we propose to define standardized measures for ABC Type I exporter structure characterization. We set conformational vectors, conftors, which describe the relative orientation of domains and can highlight structural differences. In addition, continuum electrostatics calculations were performed to characterize the energetics of membrane insertion illuminating functionally crucial regions. In summary, the proposed metrics contribute to deeper understanding of ABC membrane proteins' structural features, structure validation, and analysis of movements observed in a molecular dynamics trajectory. Moreover, the concept of standardized metrics can be applied not only to ABC membrane protein structures (http://conftors.hegelab.org). LA - English DB - MTMT ER - TY - CHAP AU - Gáspárné Csizmadia, Georgina AU - Tordai, Hedvig AU - Spagina, Zoltán AU - Hegedűs, Tamás ED - Zimányi, László TI - ABC fehérjék 3D atlasza T2 - A Magyar Biofizikai Társaság XXVI. Kongresszusa PB - Magyar Biofizikai Társaság CY - Szeged SN - 9789631294477 PY - 2017 SP - 65 UR - https://m2.mtmt.hu/api/publication/30610087 ID - 30610087 LA - Hungarian DB - MTMT ER -