Biochemistry, General Biochemistry, Genetics and Molecular Biology, Biophysics, Structural Biology
6
Scopus Publications
491
Scholar Citations
6
Scholar h-index
5
Scholar i10-index
Scopus Publications
NMR Structural Characterization of SARS-CoV-2 ORF6 Reveals an N-Terminal Membrane Anchor Martí Ninot-Pedrosa, Gyula Pálfy, Hafez Razmazma, Jackson Crowley, Marie-Laure Fogeron, Beate Bersch, Alexander Barnes, Bernhard Brutscher, Luca Monticelli, Anja Böckmann, Beat H. Meier, Lauriane Lecoq Journal of the American Chemical Society, 2025 SARS-CoV-2, the virus responsible for the COVID-19 pandemic, encodes several accessory proteins, among which ORF6, a potent interferon inhibitor, is recognized as one of the most cytotoxic. Here, we investigated the structure, oligomeric state, and membrane interactions of ORF6 using NMR spectroscopy and molecular dynamics simulations. Using chemical-shift-ROSETTA, we show that ORF6 in proteoliposomes adopts a straight α-helical structure with an extended, rigid N-terminal part and flexible C-terminal residues. Cross-linking experiments indicate that ORF6 forms oligomers within lipid bilayers, and paramagnetic spin labeling suggests an antiparallel arrangement in its multimers. The amphipathic ORF6 helix establishes multiple contacts with the membrane surface with its N-terminal residues acting as membrane anchors. Our work demonstrates that ORF6 is an integral monotopic membrane protein and provides key insights into its conformation and the importance of the N-terminal region for the interaction with the membrane.
Comprehensive Fragment Screening of the SARS-CoV-2 Proteome Explores Novel Chemical Space for Drug Development Hannes Berg, Maria A. Wirtz Martin, Nadide Altincekic, Islam Alshamleh, Jasleen Kaur Bains, Julius Blechar, Betül Ceylan, Vanessa de Jesus, Karthikeyan Dhamotharan, Christin Fuks, Santosh L. Gande, Bruno Hargittay, Katharina F. Hohmann, Marie T. Hutchison, Sophie Marianne Korn, Robin Krishnathas, Felicitas Kutz, Verena Linhard, Tobias Matzel, Nathalie Meiser, Anna Niesteruk, Dennis J. Pyper, Linda Schulte, Sven Trucks, Kamal Azzaoui, Marcel J. J. Blommers, Yojana Gadiya, Reagon Karki, Andrea Zaliani, Philip Gribbon, Marcius da Silva Almeida, Cristiane Dinis Anobom, Anna L. Bula, Matthias Bütikofer, Ícaro Putinhon Caruso, Isabella Caterina Felli, Andrea T. Da Poian, Gisele Cardoso de Amorim, Nikolaos K. Fourkiotis, Angelo Gallo, Dhiman Ghosh, Francisco Gomes‐Neto, Oksana Gorbatyuk, Bing Hao, Vilius Kurauskas, Lauriane Lecoq, Yunfeng Li, Nathane Cunha Mebus‐Antunes, Miguel Mompeán, Thais Cristtina Neves‐Martins, Martí Ninot‐Pedrosa, Anderson S. Pinheiro, Letizia Pontoriero, Yulia Pustovalova, Roland Riek, Angus J. Robertson, Marie Jose Abi Saad, Miguel Á. Treviño, Aikaterini C. Tsika, Fabio C. L. Almeida, Ad Bax, Katherine Henzler‐Wildman, Jeffrey C. Hoch, Kristaps Jaudzems, Douglas V. Laurents, Julien Orts, Roberta Pierattelli, Georgios A. Spyroulias, Elke Duchardt‐Ferner, Jan Ferner, Boris Fürtig, Martin Hengesbach, Frank Löhr, Nusrat Qureshi, Christian Richter, Krishna Saxena, Andreas Schlundt, Sridhar Sreeramulu, Anna Wacker, Julia E. Weigand, Julia Wirmer‐Bartoschek, Jens Wöhnert, Harald Schwalbe Angewandte Chemie International Edition, 2022 SARS‐CoV‐2 (SCoV2) and its variants of concern pose serious challenges to the public health. The variants increased challenges to vaccines, thus necessitating for development of new intervention strategies including anti‐virals. Within the international Covid19‐NMR consortium, we have identified binders targeting the RNA genome of SCoV2. We established protocols for the production and NMR characterization of more than 80 % of all SCoV2 proteins. Here, we performed an NMR screening using a fragment library for binding to 25 SCoV2 proteins and identified hits also against previously unexplored SCoV2 proteins. Computational mapping was used to predict binding sites and identify functional moieties (chemotypes) of the ligands occupying these pockets. Striking consensus was observed between NMR‐detected binding sites of the main protease and the computational procedure. Our investigation provides novel structural and chemical space for structure‐based drug design against the SCoV2 proteome.
Large-Scale Recombinant Production of the SARS-CoV-2 Proteome for High-Throughput and Structural Biology Applications Nadide Altincekic, Sophie Marianne Korn, Nusrat Shahin Qureshi, Marie Dujardin, Martí Ninot-Pedrosa, Rupert Abele, Marie Jose Abi Saad, Caterina Alfano, Fabio C. L. Almeida, Islam Alshamleh, Gisele Cardoso de Amorim, Thomas K. Anderson, Cristiane D. Anobom, Chelsea Anorma, Jasleen Kaur Bains, Adriaan Bax, Martin Blackledge, Julius Blechar, Anja Böckmann, Louis Brigandat, Anna Bula, Matthias Bütikofer, Aldo R. Camacho-Zarco, Teresa Carlomagno, Icaro Putinhon Caruso, Betül Ceylan, Apirat Chaikuad, Feixia Chu, Laura Cole, Marquise G. Crosby, Vanessa de Jesus, Karthikeyan Dhamotharan, Isabella C. Felli, Jan Ferner, Yanick Fleischmann, Marie-Laure Fogeron, Nikolaos K. Fourkiotis, Christin Fuks, Boris Fürtig, Angelo Gallo, Santosh L. Gande, Juan Atilio Gerez, Dhiman Ghosh, Francisco Gomes-Neto, Oksana Gorbatyuk, Serafima Guseva, Carolin Hacker, Sabine Häfner, Bing Hao, Bruno Hargittay, K. Henzler-Wildman, Jeffrey C. Hoch, Katharina F. Hohmann, Marie T. Hutchison, Kristaps Jaudzems, Katarina Jović, Janina Kaderli, Gints Kalniņš, Iveta Kaņepe, Robert N. Kirchdoerfer, John Kirkpatrick, Stefan Knapp, Robin Krishnathas, Felicitas Kutz, Susanne zur Lage, Roderick Lambertz, Andras Lang, Douglas Laurents, Lauriane Lecoq, Verena Linhard, Frank Löhr, Anas Malki, Luiza Mamigonian Bessa, Rachel W. Martin, Tobias Matzel, Damien Maurin, Seth W. McNutt, Nathane Cunha Mebus-Antunes, Beat H. Meier, Nathalie Meiser, Miguel Mompeán, Elisa Monaca, Roland Montserret, Laura Mariño Perez, Celine Moser, Claudia Muhle-Goll, Thais Cristtina Neves-Martins, Xiamonin Ni, Brenna Norton-Baker, Roberta Pierattelli, Letizia Pontoriero, Yulia Pustovalova, Oliver Ohlenschläger, Julien Orts, Andrea T. Da Poian, Dennis J. Pyper, Christian Richter, Roland Riek, Chad M. Rienstra, Angus Robertson, Anderson S. Pinheiro, Raffaele Sabbatella, Nicola Salvi, Krishna Saxena, Linda Schulte, Marco Schiavina, Harald Schwalbe, Mara Silber, Marcius da Silva Almeida, Marc A. Sprague-Piercy, Georgios A. Spyroulias, Sridhar Sreeramulu, Jan-Niklas Tants, Kaspars Tārs, Felix Torres, Sabrina Töws, Miguel Á. Treviño, Sven Trucks, Aikaterini C. Tsika, Krisztina Varga, Ying Wang, Marco E. Weber, Julia E. Weigand, Christoph Wiedemann, Julia Wirmer-Bartoschek, Maria Alexandra Wirtz Martin, Johannes Zehnder, Martin Hengesbach, Andreas Schlundt Frontiers in Molecular Biosciences, 2021 The highly infectious disease COVID-19 caused by the Betacoronavirus SARS-CoV-2 poses a severe threat to humanity and demands the redirection of scientific efforts and criteria to organized research projects. The international COVID19-NMR consortium seeks to provide such new approaches by gathering scientific expertise worldwide. In particular, making available viral proteins and RNAs will pave the way to understanding the SARS-CoV-2 molecular components in detail. The research in COVID19-NMR and the resources provided through the consortium are fully disclosed to accelerate access and exploitation. NMR investigations of the viral molecular components are designated to provide the essential basis for further work, including macromolecular interaction studies and high-throughput drug screening. Here, we present the extensive catalog of a holistic SARS-CoV-2 protein preparation approach based on the consortium’s collective efforts. We provide protocols for the large-scale production of more than 80% of all SARS-CoV-2 proteins or essential parts of them. Several of the proteins were produced in more than one laboratory, demonstrating the high interoperability between NMR groups worldwide. For the majority of proteins, we can produce isotope-labeled samples of HSQC-grade. Together with several NMR chemical shift assignments made publicly available on covid19-nmr.com, we here provide highly valuable resources for the production of SARS-CoV-2 proteins in isotope-labeled form.
Alzheimer´s disease-associated aβ42 peptide: Expression and purification for NMR structural studies Montserrat Serra-Batiste, Raquel Garcia-Castellanos, Marti Ninot-Pedrosa, Bernat Serra-Vidal, Nicholas Simon Berrow, Natalia Carulla Current Chemical Biology, 2017 Background: The aggregation of the amyloid-beta peptide (Aβ) in the brain is strongly associated with Alzheimer´s disease (AD). However, the heterogeneous and transient nature of this process has prevented identification of the exact molecular form of Aβ responsible for the neurotoxicity observed in this disease. Therefore, characterizing Aβ aggregation is of utmost importance in the field of AD. Nuclear magnetic resonance spectroscopy (NMR) is a technique that holds great potential to achieve this goal. However, it requires the use of specific labels introduced through recombinant expression of Aβ. Keywords: Alzheimer's disease, Aβ42 peptide, isotope labeling, NMR, soluble expression, SUMO.
Aβ42 assembles into specific β-barrel pore-forming oligomers in membrane-mimicking environments Montserrat Serra-Batiste, Martí Ninot-Pedrosa, Mariam Bayoumi, Margarida Gairí, Giovanni Maglia, Natàlia Carulla Proceedings of the National Academy of Sciences of the United States of America, 2016 Significance Numerous reports indicate that amyloid-β peptide (Aβ) oligomers, considered the pathogenic molecular form of Aβ in Alzheimer´s disease (AD), exert their neurotoxicity within the membrane. Therefore, it is critical to characterize them in such an environment. Here, we worked with two major Aβ variants and handled them as if they were membrane proteins. By doing so, we found that the Aβ variant most strongly linked to AD assembled into stable Aβ oligomers that adopted a specific structure and incorporated into membranes as pores, a feature linked to neurotoxicity. Having access to pore-forming Aβ oligomers with such a specific structure offers unique opportunities to fully characterize them and establish their involvement in AD.
RECENT SCHOLAR PUBLICATIONS
NMR structural characterization of SARS-coV-2 ORF6 reveals an N-terminal membrane anchor M Ninot-Pedrosa, G Pálfy, H Razmazma, J Crowley, ML Fogeron, ... Journal of the American Chemical Society 147 (21), 17668-17681 , 2025 2025.0 Citations: 3
Analysis of the structure and interactions of the SARS-CoV-2 ORF7b accessory protein MH Nguyen, G Palfy, ML Fogeron, M Ninot Pedrosa, J Zehnder, V Rimal, ... Proceedings of the National Academy of Sciences 121 (46), e2407731121 , 2024 2024.0 Citations: 11
Comprehensive fragment screening of the SARS‐CoV‐2 proteome explores novel chemical space for drug development H Berg, MA Wirtz Martin, N Altincekic, I Alshamleh, J Kaur Bains, ... Angewandte Chemie International Edition 61 (46), e202205858 , 2022 2022.0 Citations: 24
Large-scale recombinant production of the SARS-CoV-2 proteome for high-throughput and structural biology applications N Altincekic, SM Korn, NS Qureshi, M Dujardin, M Ninot-Pedrosa, R Abele, ... Frontiers in molecular biosciences 8, 653148 , 2021 2021.0 Citations: 55
SARS-CoV-2 ORF7b: is a bat virus protein homologue a major cause of COVID-19 symptoms? ML Fogeron, R Montserret, J Zehnder, MH Nguyen, M Dujardin, ... BiorXiV, 2021.02. 05.428650 , 2021 2021.0 Citations: 25
Large-scale recombinant production of the SARS-CoV-2 proteome for high-throughput and structural biology applications. Front Mol Biosci 8, 89 N Altincekic, SM Korn, NS Qureshi, M Dujardin, M Ninot-Pedrosa, R Abele 2021.0 Citations: 7
Preparation of a well-defined and stable β-barrel pore-forming Aβ42 oligomer M Serra-Batiste, M Ninot-Pedrosa, E Puig, S Ciudad, M Gairí, N Carulla Amyloid Proteins: Methods and Protocols, 13-22 , 2018 2018.0 Citations: 5
Towards the validation of a druggable amyloid-beta oligomer as a target for Alzheimer´ s disease= Cap a la validació d’un oligomer de beta-amiloide com a diana en la malaltia d … M Ninot Pedrosa Universitat de Barcelona , 2018 2018.0
Alzheimer's Disease-associated Aβ42 Peptide: Expression and Purification for NMR Structural Studies M Serra-Batiste, R Garcia-Castellanos, M Ninot-Pedrosa, B Serra-Vidal, ... Current Chemical Biology 11 (1), 50-62 , 2017 2017.0 Citations: 6
Aβ42 assembles into specific β-barrel pore-forming oligomers in membrane-mimicking environments M Serra-Batiste, M Ninot-Pedrosa, M Bayoumi, M Gairí, G Maglia, ... Proceedings of the National Academy of Sciences 113 (39), 10866-10871 , 2016 2016.0 Citations: 350
Micelles promote A beta 42 assembly into pore-forming oligomers M Serra-Batiste, MMA Bayoumi, M Gairi, M Ninot-Pedrosa, G Maglia, ... Protein Science 24, 17-17 , 2015 2015.0
CL; Alshamleh, I.; de Amorim, GC; Anderson, TK; Anobom, C N Altincekic, SM Korn, NS Qureshi, M Dujardin, M Ninot-Pedrosa, R Abele, ... D , 0 Citations: 5
MOST CITED SCHOLAR PUBLICATIONS
Aβ42 assembles into specific β-barrel pore-forming oligomers in membrane-mimicking environments M Serra-Batiste, M Ninot-Pedrosa, M Bayoumi, M Gairí, G Maglia, ... Proceedings of the National Academy of Sciences 113 (39), 10866-10871 , 2016 2016.0 Citations: 350
Large-scale recombinant production of the SARS-CoV-2 proteome for high-throughput and structural biology applications N Altincekic, SM Korn, NS Qureshi, M Dujardin, M Ninot-Pedrosa, R Abele, ... Frontiers in molecular biosciences 8, 653148 , 2021 2021.0 Citations: 55
SARS-CoV-2 ORF7b: is a bat virus protein homologue a major cause of COVID-19 symptoms? ML Fogeron, R Montserret, J Zehnder, MH Nguyen, M Dujardin, ... BiorXiV, 2021.02. 05.428650 , 2021 2021.0 Citations: 25
Comprehensive fragment screening of the SARS‐CoV‐2 proteome explores novel chemical space for drug development H Berg, MA Wirtz Martin, N Altincekic, I Alshamleh, J Kaur Bains, ... Angewandte Chemie International Edition 61 (46), e202205858 , 2022 2022.0 Citations: 24
Analysis of the structure and interactions of the SARS-CoV-2 ORF7b accessory protein MH Nguyen, G Palfy, ML Fogeron, M Ninot Pedrosa, J Zehnder, V Rimal, ... Proceedings of the National Academy of Sciences 121 (46), e2407731121 , 2024 2024.0 Citations: 11
Large-scale recombinant production of the SARS-CoV-2 proteome for high-throughput and structural biology applications. Front Mol Biosci 8, 89 N Altincekic, SM Korn, NS Qureshi, M Dujardin, M Ninot-Pedrosa, R Abele 2021.0 Citations: 7
Alzheimer's Disease-associated Aβ42 Peptide: Expression and Purification for NMR Structural Studies M Serra-Batiste, R Garcia-Castellanos, M Ninot-Pedrosa, B Serra-Vidal, ... Current Chemical Biology 11 (1), 50-62 , 2017 2017.0 Citations: 6
Preparation of a well-defined and stable β-barrel pore-forming Aβ42 oligomer M Serra-Batiste, M Ninot-Pedrosa, E Puig, S Ciudad, M Gairí, N Carulla Amyloid Proteins: Methods and Protocols, 13-22 , 2018 2018.0 Citations: 5
CL; Alshamleh, I.; de Amorim, GC; Anderson, TK; Anobom, C N Altincekic, SM Korn, NS Qureshi, M Dujardin, M Ninot-Pedrosa, R Abele, ... D , 0 Citations: 5
NMR structural characterization of SARS-coV-2 ORF6 reveals an N-terminal membrane anchor M Ninot-Pedrosa, G Pálfy, H Razmazma, J Crowley, ML Fogeron, ... Journal of the American Chemical Society 147 (21), 17668-17681 , 2025 2025.0 Citations: 3
Towards the validation of a druggable amyloid-beta oligomer as a target for Alzheimer´ s disease= Cap a la validació d’un oligomer de beta-amiloide com a diana en la malaltia d … M Ninot Pedrosa Universitat de Barcelona , 2018 2018.0
Micelles promote A beta 42 assembly into pore-forming oligomers M Serra-Batiste, MMA Bayoumi, M Gairi, M Ninot-Pedrosa, G Maglia, ... Protein Science 24, 17-17 , 2015 2015.0
