Article
Biochemistry & Molecular Biology
Silja Lucia Salscheider, Sarah Gerlich, Alfredo Cabrera-Orefice, Esra Peker, Robin Alexander Rothemann, Lena Maria Murschall, Yannik Finger, Karolina Szczepanowska, Zeinab Alsadat Ahmadi, Sergio Guerrero-Castillo, Alican Erdogan, Mark Becker, Muna Ali, Markus Habich, Carmelina Petrungaro, Nele Burdina, Guenter Schwarz, Merlin Klussmann, Ines Neundorf, David A. Stroud, Michael T. Ryan, Aleksandra Trifunovic, Ulrich Brandt, Jan Riemer
Summary: The study shows that AIFM1 and MIA40/CHCHD4 cooperate beyond the import of MIA40/CHCHD4 and form a stable complex in vitro, in different cell lines, and in tissues. AIFM1 serves two overlapping functions, importing MIA40/CHCHD4 and constituting an integral part of the disulfide relay.
Article
Biochemistry & Molecular Biology
Sarah F. Ruidiaz, Jesper E. Dreier, Rasmus Hartmann-Petersen, Birthe B. Kragelund
Summary: Two IDPs, DSS1 and CSNAP, have differences in structure and function, with even subtle sequence variance potentially leading to different functional traits. These traits may impact their ability to engage in multiple interactions, thus affecting their interactome sizes.
Article
Biochemistry & Molecular Biology
Estella A. Newcombe, Catarina B. Fernandes, Jeppe E. Lundsgaard, Inna Brakti, Kresten Lindorff-Larsen, Annette E. Langkilde, Karen Skriver, Birthe B. Kragelund
Summary: Motifs within proteins help categorize their functions；Intrinsically disordered proteins (IDPs) rich in short linear motifs with various roles；Study found calcium-binding motifs in IDPs may serve various underreported structural and functional roles.
Article
Biochemistry & Molecular Biology
Letizia Pontoriero, Marco Schiavina, Sophie M. Korn, Andreas Schlundt, Roberta Pierattelli, Isabella C. Felli
Summary: This study identifies the crucial role of the intrinsically disordered regions (IDRs) of the SARS-CoV-2 nucleocapsid (N) protein in RNA recognition. By using NMR spectroscopy, the researchers provide atomic-level details of the interplay between folded and disordered regions of N during RNA interaction, offering insights into the replication process of the SARS-CoV-2 virus.
Article
Chemistry, Multidisciplinary
Adriana Savastano, David Flores, Harindranath Kadavath, Jacek Biernat, Eckhard Mandelkow, Markus Zweckstetter
Summary: Phosphorylation of tau at specific epitopes can affect its ability to nucleate microtubule bundles during LLPS, while phosphorylation at other sites does not inhibit tubulin assembly from tau droplets. This suggests that IDP phosphorylation may be a widely used mechanism for regulating condensate-mediated cytoskeletal assembly.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Genetics & Heredity
Syed-Rehan A. Hussain, Mehmet E. Yalvac, Benedict Khoo, Sigrid Eckardt, K. John McLaughlin
Summary: Gene editing of the mitochondrial genome using CRISPR-Cas9 system faces challenges due to inefficient delivery of guide RNA and Cas9 into mitochondria. This study demonstrates successful gene editing in mitochondrial DNA by appending a targeting RNA to a stem-loop element and expressing Cas9 with a mitochondrial localization sequence. The results suggest potential therapeutic applications of CRISPR-Cas9 for mitochondrial-related diseases.
FRONTIERS IN GENETICS
(2021)
Article
Biology
Raul Araya-Secchi, Katrine Bugge, Pernille Seiffert, Amalie Petry, Gitte W. Haxholm, Kresten Lindorff-Larsen, Stine Falsig Pedersen, Lise Arleth, Birthe B. Kragelund
Summary: This study investigates the role of lipids in PRLR signaling and finds that co-structure formation locks the disordered domain of PRLR in an extended structure, enabling signal relay.
Article
Biochemistry & Molecular Biology
Zdenek Kejik, Nela Koubkova, Lucie Krcova, David Sykora, Nikita Abramenkoa, Katerina Vesela, Robert Kaplanek, Jan Hajduch, Magdalena Houdova Megova, Petr Busek, Aleksi Sedo, Lukas Lacina, Karel Smetana Jr, Pavel Martasek, Milan Jakubek
Summary: Pentamethinium indolium salts have high affinity for mitochondrial phospholipids and exhibit changes in fluorescence properties. Especially cPMS shows potential applications in mitochondrial imaging and as cytotoxic agents against cancer cells.
BIOORGANIC CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Marco Schiavina, Letizia Pontoriero, Giuseppe Tagliaferro, Roberta Pierattelli, Isabella C. Felli
Summary: This study aimed to investigate the interaction mechanism between the nucleocapsid protein of the SARS-CoV-2 virus and the polyanion heparin. Using nuclear magnetic resonance and isothermal titration calorimetry, it was found that the NTD construct of N plays a key role in the interaction with heparin, highlighting the importance of IDRs in increasing affinity.
Article
Chemistry, Multidisciplinary
Dachi Wang, Wenxi Wang, Le Fang, Lubin Qi, Yuchao Zhang, Jie Liu, Yuxin Liang, Hongwei Yang, Mengjie Wang, Xiaojian Wei, Ruibin Jiang, Yuan Liu, Wei Zhou, Xiaohong Fang
Summary: Targeted protein degradation (TPD) is an emerging technique for regulating proteins. However, current TPD methods are ineffective against target proteins in membrane organelles like mitochondria. In this study, a mitochondria-targeting protease chimera (MtPTAC) was developed, which can specifically degrade target proteins inside mitochondria. MtPTAC activates the hydrolase activity of mitochondrial caseinolytic protease P (ClpP) and brings target proteins in proximity with ClpP. The study demonstrates the powerful proteolytic ability and potential application of MtPTAC in tumor treatment.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Biochemistry & Molecular Biology
Gregory-Neal W. Gomes, Ashley Namini, Claudiu C. Gradinaru
Summary: In this study, the conformational ensembles of the disordered protein Sic1 were calculated and compared. The physics-based generation of initial ensembles was found to be important, and insights were provided for designing new experiments. The differences between ensembles optimized from different priors were greater compared to using the same prior with different optimization methods.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Jesper E. Dreier, Andreas Prestel, Joao M. Martins, Sebastian S. Brondum, Olaf Nielsen, Anna E. Garbers, Hiroaki Suga, Wouter Boomsma, Joseph M. Rogers, Rasmus Hartmann-Petersen, Birthe B. Kragelund
Summary: A disordered ubiquitin-binding motif (DisUBM) has been discovered, which can remain disordered when bound and has functions in degradation and transcription. The motif relies on aromatic and negatively charged residues, has low and moldable affinity, and can increase the interaction surface with ubiquitin. DisUBMs can emerge from unbiased screening of randomized peptide libraries.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Chang Liu, Manxing Zou, Jianguo Zuo, Huanfang Xie, Weiping Lyu, Jian Xu, Feng Feng, Haopeng Sun, Wenyuan Liu, Xueyang Jiang
Summary: The FDA has approved donepezil, a selective AChE inhibitor, as a first-line drug for mild to moderate AD, but patients taking donepezil often experience peripheral side effects. This study introduces a series of novel thiazole salt AChE inhibitors with nanomolar inhibitory effect on human AChE. Thiamine disulfide prodrugs based on these inhibitors are developed and shown to be converted into thiazole salt AChE inhibitors in the brain, with high brain exposure and stronger inhibitory effects compared to intestinal AChE in vivo. This study provides a possible basis for centrally targeted thiazole salt inhibitors in the treatment of neurodegenerative diseases.
BIOORGANIC CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Nina L. Jacobsen, Magnus Bloch, Peter S. Millard, Sarah F. Ruidiaz, Jonas D. Elsborg, Wouter Boomsma, Ruth Hendus-Altenburger, Rasmus Hartmann-Petersen, Birthe B. Kragelund
Summary: This study found that Schizosaccharomyces pombe Dss1 is phosphorylated by casein kinase 2 at three threonine sites in its linker region. The phosphorylation does not affect its ubiquitin binding ability, but slightly destabilizes the C-terminal alpha-helix and directly interacts with the forkhead-associated domain of the RING-FHA E3-ubiquitin ligase defective in mitosis 1 (Dma1). These phosphorylation sites are absent in human Dss1.
Review
Biochemistry & Molecular Biology
Amy Romesberg, Bennett Van Houten
Summary: Mitochondria, the ATP-generating organelles in eukaryotic cells, are prone to oxidative damage on their DNA, which can lead to mtDNA mutations and deletions and result in various diseases. While previous studies have explored the mechanism of mitochondrial dysfunction, there are limitations in the methods used. This study introduces a novel chemoptogenetic approach to precisely investigate the downstream effects of ROS-induced damage on mitochondria and mtDNA.
Review
Chemistry, Multidisciplinary
Isabella C. Felli, Roberta Pierattelli
Summary: Modern C-13 NMR has become a valuable tool for biomolecular applications, allowing for complete assignment of proteins and providing unique information. A wide range of NMR observables can be measured to characterize the structure and dynamics of proteins comprehensively.
Article
Biochemistry & Molecular Biology
Aikaterini C. Tsika, Angelo Gallo, Nikolaos K. Fourkiotis, Aikaterini I. Argyriou, Sridhar Sreeramulu, Frank Loehr, Vladimir V. Rogov, Christian Richter, Verena Linhard, Santosh L. Gande, Nadide Altincekic, Robin Krishnathas, Isam Elamri, Harald Schwalbe, Jan Wollenhaupt, Manfred S. Weiss, Georgios A. Spyroulias
Summary: Viral infection triggers molecular defense mechanisms, including ADP-ribosylation. Viral macro domains, which can reverse ADP-ribosylation, are potential pharmaceutical targets. GS-441524, a metabolite of remdesivir, selectively inhibits viral macro domains.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Hannes Berg, Maria A. Wirtz Martin, Nadide Altincekic, Islam Alshamleh, Jasleen Kaur Bains, Julius Blechar, Betul 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 Butikofer, Icaro 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 Mompean, Thais Cristtina Neves-Martins, Marti Ninot-Pedrosa, Anderson S. Pinheiro, Letizia Pontoriero, Yulia Pustovalova, Roland Riek, Angus J. Robertson, Marie Jose Abi Saad, Miguel A. Trevino, Aikaterini C. Tsika, Fabio C. L. Almeida, Ad Bax, Katherine Henzler-Wildman, Jeffrey C. Hoch, Kristaps Jaudzems, Douglas Laurents, Julien Orts, Roberta Pierattelli, Georgios A. Spyroulias, Elke Duchardt-Ferner, Jan Ferner, Boris Furtig, Martin Hengesbach, Frank Lohr, Nusrat Qureshi, Christian Richter, Krishna Saxena, Andreas Schlundt, Sridhar Sreeramulu, Anna Wacker, Julia E. Weigand, Julia Wirmer-Bartoschek, Jens Wohnert, Harald Schwalbe
Summary: This study explores novel drug design against SARS-CoV-2 through NMR screening and computational mapping. They identified multiple molecules that bind to SARS-CoV-2 proteins and studied their structural and chemical properties, providing new insights for drug development.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Biophysics
Nikolaos K. Fourkiotis, Periklis Charalampous, Aikaterini C. Tsika, Konstantina P. Kravvariti, Christos Sideras-Bisdekis, Angelo Gallo, Georgios A. Spyroulias
Summary: hPARP14 is a human ADP-ribosyl-transferase that belongs to the macroPARPs family. It contains three macro domains (MD), with MD2 and MD3 recognizing mono-ADP-ribosylated substrates. hPARP14 is involved in DNA damage repair and immune response, and is implicated in various cancers. This study reports the NMR assignment of hPARP14 MD2 and predicts its secondary structure elements.
BIOMOLECULAR NMR ASSIGNMENTS
(2022)
Article
Biophysics
Maria D. Politi, Angelo Gallo, Georgios Bouras, Maria Birkou, Bruno Canard, Bruno Coutard, Georgios A. Spyroulias
Summary: This study focused on the genome of Hepatitis E virus (HEV) and specifically on one of its proteins, HEV MD. The researchers found that HEV MD plays an important role in the interaction between the virus and the host, as well as in viral replication. They conducted a detailed structural analysis of HEV MD and discovered that its structure is similar to that of other viral macro domains.
BIOMOLECULAR NMR ASSIGNMENTS
(2023)
Article
Nanoscience & Nanotechnology
Onur Yildirim, Arshak Tsaturyan, Alessandro Damin, Stefano Nejrotti, Valentina Crocella, Angelo Gallo, Michele Remo Chierotti, Matteo Bonomo, Claudia Barolo
Summary: In this study, a novel 2D covalent organic polymer (COP), TAPB-QOT COP, is designed and synthesized. The polymer exhibits high iodine (I2) uptake capacity due to the presence of embedded sulfur sites and a conjugated scaffold. Characterization techniques confirm the high affinity between the sulfur atom in the COP and I2. The TAPB-QOT COP shows promising prospects for iodine capture with high volumetric uptake and reversibility.
ACS APPLIED MATERIALS & INTERFACES
(2023)
Article
Biochemistry & Molecular Biology
Federica Bravetti, Raffaele E. E. Russo, Simone Bordignon, Angelo Gallo, Federica Rossi, Carlo Nervi, Roberto Gobetto, Michele R. R. Chierotti
Summary: Computational approaches like Crystal Structure Prediction (CSP) have been increasingly used in crystal structure determination, providing insights into the packing of atoms and molecules in the solid state without diffraction data. The coupling of CSP with solid-state NMR (SSNMR) enhances the accuracy and performance of the predictive method, known as CSP-NMRX. This paper successfully applies CSP-NMRX to determine the crystal structure of pyridine dicarboxylic acid isomers, using mono- and bidimensional SSNMR spectra and RMSEs between experimental and computed chemical shifts.
Article
Biochemistry & Molecular Biology
Beatrice Bargagna, Sara Matteucci, Simone Ciofi-Baffoni, Francesca Camponeschi, Lucia Banci
Summary: Assembly of [4Fe-4S](2+) clusters in human cytosol requires a [2Fe-2S] cluster chaperone and an electron donor, and the mechanism of cytosolic [4Fe-4S](2+) cluster assembly is still unknown.
Article
Chemistry, Multidisciplinary
Federica Bravetti, Lukas Tapmeyer, Kathrin Skorodumov, Edith Alig, Stefan Habermehl, Robert Huehn, Simone Bordignon, Angelo Gallo, Carlo Nervi, Michele R. Chierotti, Martin U. Schmidt
Summary: Leucopterin, a white pigment found in butterflies and insects, has a variable hydrate structure with 0.1 to 0.5 molecules of water per leucopterin molecule. The crystal structure of leucopterin was determined using techniques such as powder diffraction and solid-state NMR spectroscopy. The high density of leucopterin may contribute to the light-scattering properties of butterfly wings.
Biographical-Item
Biochemistry & Molecular Biology
Ineke Braakman, Stephen High, Karl Kadler, Roberto Sitia, Kostas Tokatlidis, Philip Woodman
Article
Biochemistry & Molecular Biology
Stefano Da Vela, Giovanni Saudino, Francesca Lucarelli, Lucia Banci, Dmitri I. Svergun, Simone Ciofi-Baffoni
Summary: In humans, the biosynthesis and trafficking of mitochondrial [4Fe-4S]2+ clusters is a highly coordinated process that requires a complex protein machinery. Two [2Fe-2S]2+ clusters are converted into a [4Fe-4S]2+ cluster on an ISCA1-ISCA2 complex. NFU1 is the accessory protein that first receives the [4Fe-4S]2+ cluster from the ISCA1-ISCA2 complex.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Beatrice Bargagna, Lucia Banci, Francesca Camponeschi
Summary: Multiple mitochondrial dysfunctions syndrome type 2 with hyperglycinemia (MMDS2) is a severe disorder caused by biallelic mutations in the BOLA3 gene, resulting in impaired function of mitochondrial respiratory complexes and lipoic acid-dependent enzymes. The p.His96Arg mutation in BOLA3 leads to the formation of a non-functional heterocomplex with GLRX5, preventing the assembly of a [4Fe-4S] cluster on NFU1. These findings help explain the severe phenotype observed in MMDS2.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Enrico Luchinat, Lucia Banci
Summary: In-cell NMR, a technique for studying specific macromolecules within living cells, is increasingly used for structural and mechanistic analysis of proteins and nucleic acids in complex cellular environments. It has also shown potential in early stage drug development. This Perspective highlights recent advancements and successful applications of in-cell NMR spectroscopy, particularly focusing on soluble proteins, and discusses the insights it can provide on cellular processes and drug efficacy. The challenges and future developments of in-cell NMR are also discussed.
RENDICONTI LINCEI-SCIENZE FISICHE E NATURALI
(2023)
Article
Biochemical Research Methods
Marco Schiavina, Lorenzo Bracaglia, Maria Anna Rodella, Rainer Kuemmerle, Robert Konrat, Isabella Felli, Roberta Pierattelli
Summary: Nuclear magnetic resonance (NMR) spectroscopy is a powerful technique for characterizing biomolecules at atomic resolution. The availability of ultra-high-field NMR instrumentation has opened up new possibilities for studying more complex systems, such as flexible proteins and protein regions. While conducting experiments at such high field strengths comes with challenges, strategies and tricks can be employed to optimize the experiments.
Review
Chemistry, Multidisciplinary
Isabella C. Felli, Roberta Pierattelli
Summary: Modern C-13 NMR has become a valuable tool for biomolecular applications, allowing for complete protein assignment and unique information for the study of various biomolecules. Its different properties compared to H-1 provide the rationale for experiments and their applications in structural and dynamic characterization.
