TY - JOUR AU - Simon, Márton TI - Understanding impact of δF508 and G551D CFTR mutations on CFTR/PKA-c interaction JF - BIOPHYSICAL JOURNAL J2 - BIOPHYS J VL - 122 PY - 2023 IS - 3S1 SP - 112a EP - 112a SN - 0006-3495 DO - 10.1016/j.bpj.2022.11.786 UR - https://m2.mtmt.hu/api/publication/33666371 ID - 33666371 N1 - Export Date: 27 February 2023 LA - English DB - MTMT ER - TY - JOUR AU - Simon, Márton AU - Csanády, László TI - Optimization of CFTR gating through the evolution of its extracellular loops JF - JOURNAL OF GENERAL PHYSIOLOGY J2 - J GEN PHYSIOL VL - 155 PY - 2023 IS - 4 PG - 16 SN - 0022-1295 DO - 10.1085/jgp.202213264 UR - https://m2.mtmt.hu/api/publication/33636409 ID - 33636409 LA - English DB - MTMT ER - TY - JOUR AU - Simon, Márton AU - Iordanov, Iordan AU - Szöllősi, András AU - Csanády, László TI - Estimating the true stability of the prehydrolytic outward-facing state in an ABC protein. JF - ELIFE J2 - ELIFE VL - 12 PY - 2023 PG - 19 SN - 2050-084X DO - 10.7554/eLife.90736 UR - https://m2.mtmt.hu/api/publication/34232792 ID - 34232792 AB - CFTR, the anion channel mutated in cystic fibrosis patients, is a model ABC protein whose ATP-driven conformational cycle is observable at single-molecule level in patch-clamp recordings. Bursts of CFTR pore openings are coupled to tight dimerization of its two nucleotide-binding domains (NBDs) and in wild-type (WT) channels are mostly terminated by ATP hydrolysis. The slow rate of non-hydrolytic closure - which determines how tightly bursts and ATP hydrolysis are coupled - is unknown, as burst durations of catalytic site mutants span a range of ~200-fold. Here, we show that Walker A mutation K1250A, Walker B mutation D1370N, and catalytic glutamate mutations E1371S and E1371Q all completely disrupt ATP hydrolysis. True non-hydrolytic closing rate of WT CFTR approximates that of K1250A and E1371S. That rate is slowed ~15-fold in E1371Q by a non-native inter-NBD H-bond, and accelerated ~15-fold in D1370N. These findings uncover unique features of the NBD interface in human CFTR. LA - English DB - MTMT ER - TY - THES AU - Simon, Márton TI - A CFTR anioncsatorna extracelluláris régiójának a csatorna működésére gyakorolt hatása PY - 2023 DO - 10.14753/SE.2023.2832 UR - https://m2.mtmt.hu/api/publication/34443688 ID - 34443688 LA - Hungarian DB - MTMT ER - TY - JOUR AU - Simon, Márton AU - Bartus, Éva AU - Mag, Beáta Zsófia AU - Boros, Eszter AU - Roszjár, Lea AU - Gógl, Gergő AU - Travé, Gilles AU - Martinek, Tamás AU - Nyitray, László TI - Promiscuity mapping of the S100 protein family using a high-throughput holdup assay JF - SCIENTIFIC REPORTS J2 - SCI REP VL - 12 PY - 2022 IS - 1 PG - 11 SN - 2045-2322 DO - 10.1038/s41598-022-09574-2 UR - https://m2.mtmt.hu/api/publication/32777033 ID - 32777033 N1 - These authors contributed equally: Márton A. Simon and Éva Bartus LA - English DB - MTMT ER - TY - CHAP AU - Simon, Márton AU - Nyitray, László ED - Borg, Jean-Paul TI - Dynamic Control of Signaling by Phosphorylation of PDZ Binding Motifs T2 - PDZ Mediated Interactions VL - 2256 PB - Springer Boston CY - New York, New York SN - 9781071611654 T3 - Methods in Molecular Biology, ISSN 1064-3745 ; 2256. PY - 2021 SP - 179 EP - 192 PG - 14 DO - 10.1007/978-1-0716-1166-1_11 UR - https://m2.mtmt.hu/api/publication/33787387 ID - 33787387 N1 - Cited By :1 Export Date: 23 August 2021 Correspondence Address: Nyitray, L.; Department of Biochemistry, Hungary; email: nyitray@elte.hu Chemicals/CAS: protein serine threonine kinase; MAST2 protein, human; Microtubule-Associated Proteins; Protein-Serine-Threonine Kinases; Ribosomal Protein S6 Kinases, 90-kDa; RPS6KA1 protein, human Funding details: Nemzeti Kutatási Fejlesztési és Innovációs Hivatal, NKFIH, K119359 Funding details: National Research, Development and Innovation Office, TKP2020-IKA-05 Funding text 1: We thank Dr. Gerg? G?gl for reading the manuscript. We also thank Vikt?ria Bilics for contributing in the FP measurement. This work was supported by the National Research, Development and Innovation Office (NKFIH) grants K119359 (to LN). MAS was supported through the New National Excellence Program of the Hungarian Ministry of Human Capacities. Project no. 2018-1.2.1-NKP-2018-00005 has been implemented with the support provided from the National Research, Development and Innovation Fund of Hungary, financed under the 2018-1.2.1-NKP funding scheme. This work was completed in the ELTE Thematic Excellence Programm 2020 Supperted by the Nation Research, Development and Innovation Office (TKP2020-IKA-05) Funding text 2: We thank Dr. Gergo˝ Gógl for reading the manuscript. We also thank Viktória Bilics for contributing in the FP measurement. This work was supported by the National Research, Development and Innovation Office (NKFIH) grants K119359 (to LN). MAS was supported through the New National Excellence Program of the Hungarian Ministry of Human Capacities. Project no. 2018-1.2.1-NKP-2018-00005 has been implemented with the support provided from the National Research, Development and Innovation Fund of Hungary, financed under the 2018-1.2.1-NKP funding scheme. This work was completed in the ELTE Thematic Excellence Programm 2020 Supperted by the Nation Research, Development and Innovation Office (TKP2020-IKA-05) AB - The dynamic regulation of protein-protein interactions (PPIs) involves phosphorylation of short liner motifs in disordered protein regions modulating binding affinities. The ribosomal-S6-kinase 1 is capable of binding to scaffold proteins containing PDZ domains through a PDZ-binding motif (PBM) located at the disordered C-terminus of the kinase. Phosphorylation of the PBM dramatically changes the interactome of RSK1 with PDZ domains exerting a fine-tuning mechanism to regulate PPIs. Here we present in detail highly effective biophysical (fluorescence polarization, isothermal calorimetry) and cellular (proteinfragment complementation) methods to study the effect of phosphorylation on RSK1-PDZ interactions that can be also applied to investigate phosphoregulation of other PPIs in signaling pathways. LA - English DB - MTMT ER - TY - JOUR AU - Simon, Márton AU - Csanády, László TI - Molecular pathology of the R117H cystic fibrosis mutation is explained by loss of a hydrogen bond JF - ELIFE J2 - ELIFE VL - 10 PY - 2021 PG - 19 SN - 2050-084X DO - 10.7554/eLife.74693 UR - https://m2.mtmt.hu/api/publication/32573094 ID - 32573094 AB - The phosphorylation-activated anion channel cystic fibrosis transmembrane conductance regulator (CFTR) is gated by an ATP hydrolysis cycle at its two cytosolic nucleotide-binding domains, and is essential for epithelial salt-water transport. A large number of CFTR mutations cause cystic fibrosis. Since recent breakthrough in targeted pharmacotherapy, CFTR mutants with impaired gating are candidates for stimulation by potentiator drugs. Thus, understanding the molecular pathology of individual mutations has become important. The relatively common R117H mutation affects an extracellular loop, but nevertheless causes a strong gating defect. Here, we identify a hydrogen bond between the side chain of arginine 117 and the backbone carbonyl group of glutamate 1124 in the cryo-electronmicroscopic structure of phosphorylated, ATP-bound CFTR. We address the functional relevance of that interaction for CFTR gating using macroscopic and microscopic inside-out patch-clamp recordings. Employing thermodynamic double-mutant cycles, we systematically track gating-state-dependent changes in the strength of the R117-E1124 interaction. We find that the H-bond is formed only in the open state, but neither in the short-lived 'flickery' nor in the long-lived 'interburst' closed state. Loss of this H-bond explains the strong gating phenotype of the R117H mutant, including robustly shortened burst durations and strongly reduced intraburst open probability. The findings may help targeted potentiator design. LA - English DB - MTMT ER - TY - GEN AU - Simon, Márton AU - Bartus, Éva AU - Mag, Beáta Zsófia AU - Boros, Eszter AU - Roszjár, Lea AU - Gógl, Gergő AU - Travé, Gilles AU - Martinek, Tamás AU - Nyitray, László TI - Binding Profile Mapping of the S100 Protein Family Using a High-throughput Local Surface Mimetic Holdup Assay PY - 2020 UR - https://m2.mtmt.hu/api/publication/31867968 ID - 31867968 AB - S100 proteins are small, typically homodimeric, vertebrate-specific EF-hand proteins that establish Ca2+-dependent protein-protein interactions in the intra- and extracellular environment and are overexpressed in various pathologies. There are about 20 distinct human S100 proteins with numerous potential partner proteins. Here, we used a quantitative holdup assay to measure affinity profiles of most members of the S100 protein family against a library of chemically synthetized foldamers. The profiles allowed us to quantitatively map the binding promiscuity of each member towards the foldamer library. Since the library was designed to systematically contain most binary natural amino acid side chain combinations, the data also provide insight into the promiscuity of each S100 protein towards all potential naturally-occurring S100 partners in the human proteome. Such information will be precious for future drug design of modulators of S100 pathological activities. LA - English DB - MTMT ER - TY - JOUR AU - Simon, Márton AU - Ecsédi, Péter AU - Kovács, M. Gábor AU - Póti, Ádám Levente AU - Reményi, Attila AU - Kardos, József AU - Gógl, Gergő AU - Nyitray, László TI - High‐throughput competitive fluorescence polarization assay reveals functional redundancy in the S100 protein family JF - FEBS JOURNAL J2 - FEBS J VL - 287 PY - 2020 IS - 13 SP - 2834 EP - 2846 PG - 13 SN - 1742-464X DO - 10.1111/febs.15175 UR - https://m2.mtmt.hu/api/publication/31009146 ID - 31009146 N1 - Funding Agency and Grant Number: National Research Development and Innovation Fund of Hungary [K119359, K120391]; New National Excellence Program of the Hungarian Ministry of Human Capacities [UNKP-18-2, UNKP-18-3]; National Research, Development and Innovation Fund of Hungary [FIEK_16-1-2016-0005, VEKOP-2.3.3-15-2016-00011, 2018-1.2.1-NKP-2018-00005, FIEK_16, VEKOP-2.3.3-15-2016, 2018-1.2.1-NKP]; National Research, Development and Innovation Office [NKFIH-1157-8/2019-DT]; Post-doctorants en France program of the Fondation ARC Funding text: We would like to thank Daniel Knapp from the Department of Plant Anatomy, ELTE, for the help in bioinformatics analyses. We would also thank Gitta Schlosser and David Papp from the Department of Analytical Chemistry, ELTE, for the help in mass spectrometry. This work was supported by the National Research Development and Innovation Fund of Hungary (K119359 to LN K120391 to JK). MAS and GG were supported through the New National Excellence Program of the Hungarian Ministry of Human Capacities (UNKP-18-2 and UNKP-18-3, respectively). We also acknowledge the FIEK_16-1-2016-0005 and VEKOP-2.3.3-15-2016-00011 grants and Project No. 2018-1.2.1-NKP-2018-00005 implemented with the support provided from the National Research, Development and Innovation Fund of Hungary, financed under the FIEK_16, VEKOP-2.3.3-15-2016, and 2018-1.2.1-NKP funding schemes, respectively. The work was completed in the ELTE Institutional Excellence Program supported by the National Research, Development and Innovation Office (NKFIH-1157-8/2019-DT). GG was supported by the Post-doctorants en France program of the Fondation ARC. WoS:hiba:000505283400001 2020-03-09 18:44 cikkazonosító nem egyezik LA - English DB - MTMT ER - TY - JOUR AU - Tököli, Attila AU - Mag, Beáta Zsófia AU - Bartus, Éva AU - Wéber, Edit AU - Szakonyi, Gerda AU - Simon, Márton AU - Czibula, Ágnes AU - Monostori, Éva AU - Nyitray, László AU - Martinek, Tamás TI - Proteomimetic surface fragments distinguish targets by function JF - CHEMICAL SCIENCE J2 - CHEM SCI VL - 11 PY - 2020 IS - 38 SP - 10390 EP - 10398 PG - 9 SN - 2041-6520 DO - 10.1039/d0sc03525d UR - https://m2.mtmt.hu/api/publication/31598466 ID - 31598466 LA - English DB - MTMT ER - TY - JOUR AU - Gógl, Gergő AU - Biri-Kovács, Beáta AU - Durbesson, Fabien AU - Jane, Pau AU - Nomine, Yves AU - Kostmann, Camille AU - Bilics, Viktória AU - Simon, Márton AU - Reményi, Attila AU - Vincentelli, Renaud AU - Trave, Gilles AU - Nyitray, László TI - Rewiring of RSK-PDZ Interactome by Linear Motif Phosphorylation JF - JOURNAL OF MOLECULAR BIOLOGY J2 - J MOL BIOL VL - 431 PY - 2019 IS - 6 SP - 1234 EP - 1249 PG - 16 SN - 0022-2836 DO - 10.1016/j.jmb.2019.01.038 UR - https://m2.mtmt.hu/api/publication/30427214 ID - 30427214 N1 - Department of Biochemistry, ELTE Eötvös Loránd University, Budapest, Hungary Unite Mixte de Recherche (UMR) 7257, Centre National de la Recherche Scientifique (CNRS) Aix-Marseille Universite, Architecture et Fonction des Macromolécules Biologiques (AFMB), Marseille, France Equipe Labellisee Ligue 2015, Department of Integrated Structural Biology, Institut de Genetique et de Biologie Moleculaire et Cellulaire (IGBMC), INSERM U1258/CNRS UMR 7104/Universite de Strasbourg, 1 rue Laurent Fries, BP 10142, Illkirch, F-67404, France Institute of Enzymology, Research Center for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary Cited By :19 Export Date: 15 May 2023 CODEN: JMOBA Correspondence Address: Trave, G.; Equipe Labellisee Ligue 2015, 1 rue Laurent Fries, BP 10142, France; email: trave@esbs.u-strasbg.fr AB - Phosphorylation of short linear peptide motifs is a widespread process for the dynamic regulation of protein–protein interactions. However, the global impact of phosphorylation events on the protein–protein interactome is rarely addressed. The disordered C-terminal tail of ribosomal S6 kinase 1 (RSK1) binds to PDZ domain-containing scaffold proteins, and it harbors a phosphorylatable PDZ binding motif (PBM) responsive to epidermal growth factor (EGF) stimulation. Here, we examined binding of two versions of the RSK1 PBM, either phosphorylated or unphosphorylated at position −3, to almost all (95%) of the 266 PDZ domains of the human proteome. PBM phosphorylation dramatically altered the PDZ domain-binding landscape of RSK1, by strengthening or weakening numerous interactions to various degrees. The RSK-PDZome interactome analyzed in this study reveals how linear motif-based phospho-switches convey stimulus-dependent changes in the context of related network components. LA - English DB - MTMT ER - TY - CHAP AU - Kiss, Bence AU - Ecsédi, Péter AU - Simon, Márton AU - Nyitray, László ED - Heizmann, CW TI - Isolation and Characterization of S100 Protein-Protein Complexes T2 - Calcium-binding proteins of the EF-hand superfamily : from basics to medical applications VL - 1929 PB - Humana Press CY - Totowa (NJ) SN - 9781493990306 T3 - Methods in Molecular Biology, ISSN 1064-3745 ; 1929. PY - 2019 SP - 325 EP - 338 PG - 14 DO - 10.1007/978-1-4939-9030-6_21 UR - https://m2.mtmt.hu/api/publication/33787648 ID - 33787648 N1 - Cited By :6 Export Date: 14 May 2021 Correspondence Address: Nyitray, L.; Department of Biochemistry, Hungary; email: nyitray@elte.hu Chemicals/CAS: Multiprotein Complexes; S100 Proteins AB - S100 proteins are small, mostly dimeric, EF-hand Ca2+ binding proteins. Upon Ca2+ binding, a conformational change occurs resulting in the exposure of a shallow hydrophobic binding groove in each subunit. Interestingly, S100 proteins can interact with their partners in two ways: symmetrically, when the two partners identically bind into each groove, or asymmetrically, when only one partner binds to the S100 dimer occupying both binding pockets. Here we present a heterologous expression and purification protocol for all known human S100 proteins as well as for their partner peptides. Moreover, we provide a detailed description of three in vitro methods to determine the affinity, stoichiometry, and kinetics of S100 protein-protein interactions. LA - English DB - MTMT ER -