Article
Chemistry, Multidisciplinary
Liat Katrivas, Natalie Fardian-Melamed, Dvir Rotem, Danny Porath, Alexander Kotlyar
Summary: The guanine octuplex (G8)-DNA is a novel DNA structure with enhanced stiffness, mechanical and thermodynamic stability compared to its parent G4-DNA, making it a compelling candidate for molecular nanoelectronics.
ADVANCED MATERIALS
(2021)
Article
Chemistry, Multidisciplinary
Jinbo Zhu, Zhiqiang Yan, Filip Boskovic, Cally J. E. Haynes, Marion Kieffer, Jake L. Greenfield, Jin Wang, Jonathan R. Nitschke, Ulrich F. Keyser
Summary: The study demonstrates the binding between DNA G4 and a self-assembled metal-organic cage, resulting in aggregate formation that protects the DNA G4 from cleavage. Experiment results show that the cage interacts with a wide range of G4s and serves as a protective barrier for DNA G4.
Article
Chemistry, Multidisciplinary
Honghe Liu, Yu-Ning Lu, Tapas Paul, Goran Periz, Michael T. Banco, Adrian R. Ferre-D'Amare, Jeffrey D. Rothstein, Lindsey R. Hayes, Sua Myong, Jiou Wang
Summary: DHX36 is a robust positive regulator of C9orf72 RAN translation, facilitating the process by resolving repeat RNA G-quadruplex structures. It may serve as a potential target for therapeutic intervention in ALS and FTD associated with C9orf72 expansions.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Biochemistry & Molecular Biology
Haritha Asha, Petr Stadlbauer, Lara Martinez-Fernandez, Pavel Banas, Jiri Sponer, Roberto Improta, Luciana Esposito
Summary: The study investigates the structural behavior of a quadruplex helix sequence in human telomeres when one of the G bases is ionized to G(center dot+). It is found that the position of G(center dot+) influences structural rearrangements, electrostatic repulsion, and solvent exposure, providing new insights into guanine reactions. The research suggests structural determinants of reactivity and implications for understanding reactivity in other G-quadruplex topologies.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Article
Biochemistry & Molecular Biology
Corey Nelson, Tyler Mrozowich, Darren L. Gemmill, Sean M. Park, Trushar R. Patel
Summary: The study demonstrates that DEAD-box helicase DDX3X can directly interact with and unwind flaviviral TRs in vitro. Therefore, DDX3X may be further explored as a therapeutic target to inhibit Flaviviral replication.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Corey R. Nelson, Tyler Mrozowich, Sean M. Park, Simmone D'souza, Amy Henrickson, Justin R. J. Vigar, Hans-Joachim Wieden, Raymond J. Owens, Borries Demeler, Trushar R. Patel
Summary: This study demonstrates that DDX17 can directly interact with and unwind RVFV non-coding RNA regions IGR and NCR, providing important insights into the mechanism by which DDX17 restricts RVFV replication.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Multidisciplinary
Marco Campanile, Rosario Oliva, Pompea Del Vecchio, Roland Winter, Luigi Petraccone
Summary: LL-III, a natural anticancer peptide, has been found to bind to G-quadruplex structures with high affinity, which are known to be important targets in anticancer treatment.
CHEMICAL COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Rongxin Zhang, Yajun Liu, Xingxing Zhang, Ke Xiao, Yue Hou, Hongde Liu, Xiao Sun
Summary: The study profiles and depicts RNA G-quadruplexes in the human transcriptome using DMS-seq and bioinformatics pipeline, revealing their significant association with immune pathways and COVID-19-related gene sets. The bioinformatics analysis also suggests potential regulatory functions of G-quadruplexes on miRNA targeting at the whole transcriptome level. Moreover, G-quadruplexes are found to be depleted in putative, but not real, PAS-strong poly(A) sites, weakening their likelihood of being actual cleaved sites.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Xiaomei He, Jun Yuan, Yinsheng Wang
Summary: RNA guanine quadruplexes (rG4) play important roles in post-transcriptional gene expression regulation, often modulated by rG4-binding proteins. We identified multiple candidate rG4-binding proteins using a bioinformatic approach, and validated that G3BP1 can directly bind to rG4 structures with high affinity and selectivity, regulating mRNA stability through its binding with rG4 structures. Our findings suggest that pyridostatin can displace G3BP1 from mRNA in cells, particularly in the 3'-untranslated regions (3'-UTR) of mRNAs.
NUCLEIC ACIDS RESEARCH
(2021)
Review
Biochemistry & Molecular Biology
Tom Miclot, Aurane Froux, Luisa D'Anna, Emmanuelle Bignon, Stephanie Grandemange, Giampaolo Barone, Antonio Monari, Alessio Terenzi
Summary: In this review, the important studies on the interactions between G4s and peptides are examined, and the strengths and limitations of current analytic approaches are highlighted. It is found that the combined use of high-level molecular simulation techniques and experimental spectroscopy is the best way to design specifically tuned and selective peptides, thus controlling important biological functions.
Article
Chemistry, Multidisciplinary
Diana Muller, Irene Bessi, Christian Richter, Harald Schwalbe
Summary: The folding kinetics of RNA G4 and DNA G4 differ significantly during K+-induced folding, mainly due to differences in their folded conformations, especially regarding the chi angle preferences. Modified DNA G4 can achieve faster folding kinetics and monomorphic conformations similar to RNA G4 by adjusting the chi angle.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Biochemical Research Methods
Marco Caterino, Katrin Paeschke
Summary: The nucleic acid structure known as G-quadruplex (G4) plays a significant role in nucleic acid-based mechanisms that impact cellular processes. DNA G4 is well-studied, while RNA G4 is gaining attention for its role in cellular homeostasis. Proper regulation of G4 structures within cells is crucial, and helicases are important in resolving them. However, only a few rG4 unwinding helicases have been identified and characterized so far.
Article
Biochemistry & Molecular Biology
Wilfried M. Guiblet, Michael DeGiorgio, Xiaoheng Cheng, Francesca Chiaromonte, Kristin A. Eckert, Yi-Fei Huang, Kateryna D. Makova
Summary: Approximately 1% of the human genome can fold into G-quadruplexes (G4s), which are noncanonical DNA structures forming at G-rich motifs. G4s regulate key cellular processes and may be involved in replication and transcription. Their distribution, stability, and functionality vary across genomic regions, indicating potential selective pressures at play.
Article
Cell Biology
Shin-ichiro Ohno, Keiki Oikawa, Toshiaki Tsurui, Yuichirou Harada, Kana Ono, Mizumo Tateishi, Aashiq Mirza, Masakatsu Takanashi, Kosuke Kanekura, Kumiko Nagase, Yoshihisa Shimada, Yujin Kudo, Norihiko Ikeda, Takahiro Ochiya, Xiaozhong Wang, Masahiko Kuroda
Summary: CDK9 and DDX21 are identified as important transcriptional activators of RNAa, forming a complex with nuclear AGO and TNRC6A. Inhibition of DDX21 can suppress RNAa by miR-34a and other miRNAs without affecting post-transcriptional regulation, facilitating the separate analysis of RNAa and post-transcriptional regulation.
Article
Biochemistry & Molecular Biology
E. V. Marilovtseva, V. M. Studitsky
Summary: G-quadruplexes are dynamic structures whose stability depends on various factors, and they play a crucial role in multiple processes in DNA and RNA.
Article
Chemistry, Multidisciplinary
Cody Geary, Guido Grossi, Ewan K. S. McRae, Paul W. K. Rothemund, Ebbe S. Andersen
Summary: RNA origami is a framework for the modular design of nanoscaffolds that can be folded from a single strand of RNA and used to organize molecular components with nanoscale precision. The newly developed computer-aided design software has been shown to improve the folding yield of kilobase-sized RNA origami, simplifying the construction of custom RNA scaffolds for nanomedicine and synthetic biology. The design of genetically expressible RNA origami requires modeling and design tools that simultaneously consider thermodynamics, the folding pathway, sequence constraints and pseudoknot optimization.
Article
Biotechnology & Applied Microbiology
Aniel Moya-Torres, Monika Gupta, Fabian Heide, Natalie Krahn, Scott Legare, Denise Nikodemus, Thomas Imhof, Markus Meier, Manuel Koch, Jorg Stetefeld
Summary: This study provides a combination of workflows to dramatically increase protein production and improve processing results, particularly for the extracellular matrix protein Netrin-1. Through genetic engineering, cell culture system optimization, protein purification, and biophysical characterization, they were able to establish an efficient and continuous production of high-quality protein suitable for structural biology studies.
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2021)
Article
Multidisciplinary Sciences
Fabian Heide, Matthew McDougall, Candice Harder-Viddal, Roy Roshko, David Davidson, Jiandong Wu, Camila Aprosoff, Aniel Moya-Torres, Francis Lin, Jorg Stetefeld
Summary: Boron neutron capture therapy (BNCT) is a therapeutic process that utilizes Boron-10 and low energy neutrons to eliminate targeted cells, primarily used for head and neck carcinomas. A proteinaceous nanotube drug delivery system has been investigated as a potential candidate for delivering Boron-10 into cancer cells, showing promising results in experimental studies.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Scott Legare, Fabian Heide, Ben A. Bailey-Elkin, Jorg Stetefeld
Summary: This study reports the biophysical and enzymatic characterization of the coronavirus main protease (M-pro) and evaluates its suitability for high-throughput screening. The researchers developed an improved substrate for screening and discovered a framework for designing M-pro enzyme assays to facilitate the discovery and development of therapies targeting M-pro.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Clinical Neurology
Nicolai B. Grether, Felix Napravnik, Thomas Imhof, Reinhold P. Linke, Jan H. Brasen, Jessica Schmitz, Maike Dohrn, Christian Schneider, Martin K. R. Svacina, Jorg Stetefeld, Manuel Koch, Helmar C. Lehmann
Summary: The objective of this study was to assess the amyloidogenic potential of variants of uncertain significance in vitro. Results showed that transthyretin-Ala65Val had significantly higher amyloidogenic potential compared to wild-type transthyretin, while the other eight variants did not show increased amyloidogenic potential. The combination of three assays and histopathology confirmed the amyloidogenicity of transthyretin-Ala65Val.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2022)
Article
Biochemistry & Molecular Biology
Fabian Heide, Scott Legare, Vu To, Monika Gupta, Haben Gabir, Thomas Imhof, Aniel Moya-Torres, Matthew McDougall, Markus Meier, Manuel Koch, Jorg Stetefeld
Summary: This study investigates the heparin binding interface and protein dynamics of extracellular matrix protein Noggin through a combination of biophysical and computational methods, expanding the understanding of Noggin's function and providing insights for other protein systems.
Article
Chemistry, Multidisciplinary
Nestor Sampedro Vallina, Ewan K. S. McRae, Cody Geary, Ebbe Sloth Andersen
Summary: RNA nanotechnology utilizes structural modularity to create self-assembling nano-architectures with applications in medicine and synthetic biology. This study introduces the paranemic-crossover triangle (PXT) as a new and versatile building block for cotranscriptional folding and reveals high structural detail of the RNA PX interaction. The PXT is used to construct filaments, rings, and cubic structures, demonstrating its potential as a rigid self-folding domain for wireframe RNA origami architectures.
Review
Chemistry, Multidisciplinary
Fabian Heide, Joerg Stetefeld
Summary: Protein nanotubes have unique properties that make them useful in drug delivery, biosensors, and energy storage. Understanding the structural features of the cavities in nanotubes is crucial for their effective application. This review presents the chemical and physical diversity of protein nanotube cavities and their potential applications in materials science, particularly in biotechnology.
Article
Biophysics
Haben Gabir, Monika Gupta, Markus Meier, Fabian Heide, Manuel Koch, Joerg Stetefeld, Borries Demeler
Summary: NET-1 is a chemotropic ligand that plays a crucial role in signaling commissural axon migration and change in direction. It interacts with its receptor UNC-5B to switch axon growth cones from attraction to repulsion. The biophysical properties of the NET-1 + UNC-5B complex have been poorly characterized. In this study, we used multi-wavelength-AUC to separate UNC-5B from NET-1 and investigated the hydrodynamic parameters and complex formation of NET-1 and UNC-5B using both multi-wavelength and single-wavelength AUC. Our results suggest that NET-1 exists in a monomer-dimer equilibrium and forms a pH-sensitive dimer that interacts with UNC-5B in an anti-parallel orientation. UNC-5B can form heterocomplexes with both monomeric and dimeric NET-1.
EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS
(2023)
Article
Nanoscience & Nanotechnology
Ewan K. S. McRae, Helena Ostergaard Rasmussen, Jianfang Liu, Andreas Boggild, Michael T. A. Nguyen, Nestor Sampedro Vallina, Thomas Boesen, Jan Skov Pedersen, Gang Ren, Cody Geary, Ebbe Sloth Andersen
Summary: RNA origami is a method for designing RNA nanostructures that can self-assemble through co-transcriptional folding. This study uses cryogenic electron microscopy to determine the structure of RNA origami sheets and bundles, revealing structural parameters and folding principles. The study also combines sheets and bundles to construct a multidomain satellite shape and characterizes its flexibility using cryo-electron tomography.
NATURE NANOTECHNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Daniel Gussakovsky, Evan P. Booy, Mira J. F. Brown, Sean A. McKenna
Summary: This study establishes the role of nuclear SRP9/SRP14 in the transcriptional regulation of 7SL and BC200 RNA. Knockdown of SRP9/SRP14 affects the steady-state levels, decay rate, and transcriptional activity of 7SL and BC200 RNA. The findings demonstrate a novel nuclear function of SRP9/SRP14 in transcriptional regulation.
Article
Multidisciplinary Sciences
Markus Meier, Monika Gupta, Serife Akguel, Matthew McDougall, Thomas Imhof, Denise Nikodemus, Raphael Reuten, Aniel Moya-Torres, Vu To, Fraser Ferens, Fabian Heide, Gay Pauline Padilla-Meier, Philipp Kukura, Wenming Huang, Birgit Gerisch, Matthias Moergelin, Kate Poole, Adam Antebi, Manuel Koch, Joerg Stetefeld
Summary: In this study, the authors provide a molecular understanding of the interactions between netrin-1 and glycosaminoglycan chains of diverse heparan sulfate proteoglycans (HSPGs) and short heparin oligosaccharides. They demonstrate that heparin oligosaccharides significantly impact the dynamic behavior of netrin-1, inducing the formation of unknown netrin-1 filaments. These findings contribute to a better understanding of the functions of netrin-1.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Medicinal
Fabian Heide, Manuel Koch, Jorg Stetefeld
Summary: Heparan sulfate is an important component in the extracellular matrix that regulates structural and functional protein processes. Drugs that mimic heparin can disrupt protein assemblies and reduce regulatory capacities by competing with naturally occurring heparan sulfate and heparin chains. The presence of numerous heparan-sulfate-binding proteins in the extracellular matrix can have unknown pathological effects, which should be further investigated when developing clinical mimetics. This article aims to explore recent studies on heparan-sulfate-mediated protein assemblies and the effects of heparin mimetics on these complexes.
Article
Biochemistry & Molecular Biology
Rachael C. C. Kretsch, Ebbe S. S. Andersen, Janusz M. M. Bujnicki, Wah Chiu, Rhiju Das, Bingnan Luo, Benoit Masquida, Ewan K. S. McRae, Griffin M. M. Schroeder, Zhaoming Su, Joseph E. E. Wedekind, Lily Xu, Kaiming Zhang, Ivan N. N. Zheludev, John Moult, Andriy Kryshtafovych
Summary: The success of the first RNA category of the Critical Assessment of Techniques for Structure Prediction competition relied on experimental structures provided by scientists. In this article, these scientists offer a unique and valuable analysis of the predicted models, highlighting areas for improvement. All 10 RNA-only targets showed predicted structures similar to experimental ones. The prediction of RNA-protein complexes remains the biggest challenge, and considering ensemble models for flexible RNAs is proposed.
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2023)