Article
Multidisciplinary Sciences
Oscar Solis, Andrea R. Beccari, Daniela Iaconis, Carmine Talarico, Camilo A. Ruiz-Bedoya, Jerome C. Nwachukwu, Annamaria Cimini, Vanessa Castelli, Riccardo Bertini, Monica Montopoli, Veronica Cocetta, Stefano Borocci, Ingrid G. Prandi, Kelly Flavahan, Melissa Bahr, Anna Napiorkowski, Giovanni Chillemi, Masato Ooka, Xiaoping Yang, Shiliang Zhang, Menghang Xia, Wei Zheng, Jordi Bonaventura, Martin G. Pomper, Jody E. Hooper, Marisela Morales, Avi Z. Rosenberg, Kendall W. Nettles, Sanjay K. Jain, Marcello Allegretti, Michael Michaelides
Summary: This study discovered an interaction between the spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and human estrogen receptor alpha (ER alpha), and identified a highly conserved and functional nuclear receptor coregulator (NRC) LXD-like motif on the S2 sub-unit.
Article
Biochemistry & Molecular Biology
Ante Turudic, Zlatko Liber, Martina Grdisa, Jernej Jakse, Filip Varga, Zlatko Satovic
Summary: The development of next-generation sequencing technology and the increasing amount of sequencing data have made bioinformatic tools used in genome assembly important. In the final step of genome annotation, specialized tools are used to identify organelle genes and structural features, with most tools targeting chloroplast sequences.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Clinical Neurology
Takahiro Shimizu, Hiroyuki Ishiura, Manato Hara, Shota Shibata, Atsushi Unuma, Akatsuki Kubota, Kaori Sakuishi, Kiyoharu Inoue, Jun Goto, Yuji Takahashi, Yuichiro Shirota, Masashi Hamada, Jun Shimizu, Shoji Tsuji, Tatsushi Toda
Summary: This study shows the expanded clinical spectrum of OPDM1, highlighting the importance of axial muscle evaluation and suggesting genetic analysis of LRP12 in patients with very subtle oculopharyngeal symptoms.
Review
Biochemistry & Molecular Biology
Stojan Peric, Jovan Pesovic, Dusanka Savic-Pavicevic, Vidosava Rakocevic Stojanovic, Giovanni Meola
Summary: Myotonic dystrophy type 1 (DM1) is a highly variable monogenic disease with variations at the phenotypic, genetic, and epigenetic levels. The disease affects multiple systems and can occur from birth to late age. The underlying mutation is an unstable expansion of CTG repeats in the DMPK gene, with larger expansions associated with an earlier age at onset. Additionally, repeat interruptions in the CTG repeats seem to have a stabilizing effect on DM1 and are associated with local DNA methylation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemical Research Methods
Pablo Mier, Carlos A. Elena-Real, Juan Cortes, Pau Bernado, Miguel A. Andrade-Navarro
Summary: This study investigates the structure and function of poly-alanine regions in proteins, identifying glycine and proline as the most abundant amino acids within polyA and its flanking regions, which influence the α-helical conformations predicted for polyA. Additionally, the research reveals the relationship between the position of polyA in protein N-termini and their function as transit peptides.
Article
Biochemistry & Molecular Biology
Ryan Mahling, Cade R. Rahlf, Samuel C. Hansen, Matthew R. Hayden, Madeline A. Shea
Summary: FGFs and CaM directly bind to the Na-V channel and play a key role in regulating channel function, especially A-type FGFs can compete with (Ca2+)(4)-CaM for binding, thereby modulating channel function.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Paula Nazarena Arrias, Alexander Miguel Monzon, Damiano Clementel, Soroush Mozaffari, Damiano Piovesan, Andrey V. Kajava, Silvio C. E. Tosatto
Summary: Structured tandem repeat proteins (STRPs) are characterized by a modular and repetitive three-dimensional structure arrangement. Previously overlooked Box repeats, a type of STRP fold, have been identified in the DNA sliding clamp processivity factors.
JOURNAL OF STRUCTURAL BIOLOGY
(2023)
Article
Neurosciences
Stefan Hintze, Raphaela Mensel, Lisa Knaier, Benedikt Schoser, Peter Meinke
Summary: Myotonic dystrophy type 1 (DM1) is a multisystemic disorder caused by CTG-repeat expansions in the DMPK gene. Despite the lack of approved therapies, primary human DM1 myoblast cultures are a suitable model for investigating certain aspects of the pathology and for conducting first-line investigations into preclinical therapies.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Medicine, Research & Experimental
Emily E. Davey, Cecilia Legare, Lori Planco, Sharon Shaughnessy, Claudia D. Lennon, Marie-Pier Roussel, Hannah K. Shorrock, Man Hung, John Douglas Cleary, Elise Duchesne, J. Andrew Berglund
Summary: Myotonic dystrophy type 1 (DM1), caused by a CTG expansion, leads to transcriptomic dysregulation and muscle weakness. This study investigated the effects of a strength-training program on gene expression and alternative splicing in male DM1 patients. The results showed that training rescued transcriptomic defects in a patient-specific manner, and gene expression improvements were correlated with strength improvements.
Article
Urology & Nephrology
Cecilie K. Skeby, Sandra Hummelgaard, Camilla Gustafsen, Federica Petrillo, Kathrine P. Frederiksen, Ditte Olsen, Tilde Kristensen, Per Ivarsen, Peder Madsen, Erik I. Christensen, Rikke Nielsen, Henrik Birn, Simon Glerup, Kathrin Weyer
Summary: This article proposes a mechanistic coupling between proteinuria and PCSK9, showing that PCSK9 is a negative regulator of megalin and glomerular damage increases filtration of PCSK9, resulting in escalated proteinuria.
KIDNEY INTERNATIONAL
(2023)
Article
Biochemistry & Molecular Biology
Betim Karahoda, Lakhansing Pardeshi, Mevlut Ulas, Zhiqiang Dong, Niranjan Shirgaonkar, Shuhui Guo, Fang Wang, Kaeling Tan, Ozlem Sarikaya-Bayram, Ingo Bauer, Paul Dowling, Alastair B. Fleming, Brandon T. Pfannenstiel, Dianiris Luciano-Rosario, Harald Berger, Stefan Graessle, Mohamed M. Alhussain, Joseph Strauss, Nancy P. Keller, Koon Ho Wong, Ozgur Bayram
Summary: This study describes a chromatin binding complex KERS in the fungus Aspergillus nidulans, consisting of H3K4 histone demethylase KdmB, cohesin acetyltransferase EcoA, histone deacetylase RpdA, and histone reader/E3 ligase protein SntB. The KERS complex exerts promoter-specific transcriptional effects at active core promoters.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Multidisciplinary Sciences
Ahmed Al-Qahtani, Mohammed N. Al-Ahdal, Saad Alkahtani
Summary: Leishmania species cause a variety of diseases ranging from moderate to severe, impacting morbidity and mortality. The human innate immune system deals with Leishmania through the complement system, particularly the classical pathway, which is activated first due to a lag phase before the alternative pathway activation. Recognition molecule C1q binds to soluble leishmania antigens (SLA) and activates the classical pathway, leading to downregulation of cytokine and chemokine responses. This highlights the importance of potent adjuvants in SLA-mediated vaccine strategies.
JOURNAL OF KING SAUD UNIVERSITY SCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Nicklas Oesterlund, Rebecca Frankel, Andreas Carlsson, Dev Thacker, Maja Karlsson, Vanessa Matus, Astrid Graeslund, Cecilia Emanuelsson, Sara Linse
Summary: This study investigated the role of the C-terminal domain (CTD) of DNAJB6 in inhibiting the fibril formation of amyloid peptides. The CTD was found to inhibit secondary nucleation by binding to An42 fibrils, while the full-length DNAJB6 protein inhibited primary nucleation by forming coaggregates with An.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Anna Caccamo, Felix Vega de Luna, Khadija Wahni, Alexander N. Volkov, Jonathan Przybyla-Toscano, Antonello Amelii, Alexandre Kriznik, Nicolas Rouhier, Joris Messens, Claire Remacle
Summary: Recent studies have identified a novel class of ascorbate peroxidases called APX-R, with a focus on APX2 from Chlamydomonas reinhardtii in this study. Experimental results indicate that APX2 exhibits peroxidase activity with guaiacol as an electron donor, along with the ability to bind copper and heme. Evidence suggests a potential interaction between APX2 and plastocyanin, highlighting the role of APX2 in regulating copper transfer to plastocyanin.
Article
Biochemistry & Molecular Biology
Giuseppe Valerio De Gaetano, Francesco Coppolino, Germana Lentini, Agata Fama, Chiara Cullotta, Ivana Raffaele, Chiara Motta, Giuseppe Teti, Pietro Speziale, Giampiero Pietrocola, Concetta Beninati
Summary: The binding of Streptococcus pneumoniae to collagen is an important step in the development of pneumococcal infections. This study found that SSURE repeats of the PfbB protein promote interactions between pneumococci and collagen, as well as the complement component C1q. These findings provide insights into the molecular mechanisms of pneumococcal infections and suggest potential targets for controlling these infections.
MOLECULAR MICROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Jacob H. Martinsen, Daniel Saar, Catarina B. Fernandes, Benjamin Schuler, Katrine Bugge, Birthe B. Kragelund
Summary: Linker histone H1 plays a role in epigenetic regulation by binding to nucleosomes and altering chromatin structures. Recent research suggests that the number and position of charged side chains on the globular domain of H1 influence chromatin structure and gene repression. By analyzing charge variants of the globular domain, researchers found that modulating the number of charges has little effect on the structure, but affects the stability. This finding helps in understanding the function and structure of H1 histone.
Article
Biochemistry & Molecular Biology
Frederik Friis Theisen, Edoardo Salladini, Rikke Davidsen, Christina Jo Rasmussen, Lasse Staby, Birthe B. Kragelund, Karen Skriver
Summary: This study investigates the specificity in transcriptional networks using alpha alpha-hubs as a model. It reveals that although these alpha alpha-hubs share a common motif, they differ in the length, orientation, and thermodynamic profiles of accessory helices and ligand binding. Thermal stability studies indicate that the unfolding behavior and temperature sensitivity also vary among different domains. Overall, the results suggest that the structure, flexibility, and binding thermodynamics contribute to the specificity of alpha alpha hub-transcription factor binding.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Nader Al-Nakouzi, Chris Kedong Wang, Htoo Zarni Oo, Irina Nelepcu, Nada Lallous, Charlotte B. Spliid, Nastaran Khazamipour, Joey Lo, Sarah Truong, Colin Collins, Desmond Hui, Shaghayegh Esfandnia, Hans Adomat, Thomas Mandel Clausen, Tobias Gustavsson, Swati Choudhary, Robert Dagil, Eva Corey, Yuzhuo Wang, Anne Chauchereau, Ladan Fazli, Jeffrey D. Esko, Ali Salanti, Peter S. Nelson, Martin E. Gleave, Mads Daugaard
Summary: Inhibition of the androgen receptor pathway leads to the upregulation of chondroitin sulfate (CS), which promotes the growth and metastasis of prostate cancer.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Yong Jung, Cunliang Geng, Alexandre M. J. J. Bonvin, Li C. Xue, Vasant G. Honavar
Summary: Protein-protein interactions are crucial for biological function, and understanding their three-dimensional structures is essential. Computational docking is a useful alternative to experimental approaches for determining these structures, but the scoring problem still needs improvement. MetaScore is a machine-learning-based approach that uses protein-protein interfacial features to score docked conformations. It consistently outperforms traditional scoring functions and an ensemble method combining MetaScore with traditional functions achieves even better performance. Machine learning and ensemble methods can improve the accuracy of scoring protein-protein interactions.
Article
Biology
Steffie Elkjaer, Amanda D. D. Due, Lise F. F. Christensen, Frederik F. Theisen, Lasse Staby, Birthe B. B. Kragelund, Karen Skriver
Summary: Evolution-guided mutagenesis and biophysical analysis reveal that residual helical structure in the binding region of an intrinsically disordered protein regulates the lifetime of its complex by affecting its dissociation.
COMMUNICATIONS BIOLOGY
(2023)
Article
Oncology
Nanna Skeltved, Mie A. A. Nordmaj, Nicolai T. T. Berendtsen, Robert Dagil, Emilie M. R. Stormer, Nader Al-Nakouzi, Ke Jiang, Alexandra Aicher, Christopher Heeschen, Tobias Gustavsson, Swati Choudhary, Ismail Gogenur, Jan P. P. Christensen, Thor G. G. Theander, Mads Daugaard, Ali Salanti, Morten A. A. Nielsen
Summary: The malaria protein VAR2CSA has anti-tumor efficacy by binding to oncofetal chondroitin sulfate (ofCS). Combining V-aCD3 with an immune checkpoint inhibitor enhances the anti-tumor effects, leading to complete elimination of solid tumors in mice.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2023)
Letter
Biochemistry & Molecular Biology
Kaare Teilum, Johan G. Olsen, Birthe B. Kragelund
Article
Biochemistry & Molecular Biology
Siri C. van Keulen, Alexandre M. J. J. Bonvin
Summary: The increase in protein sequences and structures has allowed for the use of bioinformatics approaches to predict residue-residue interactions. Multiple sequence alignments are commonly used in contact predictions but often produce false positives, which can affect the accuracy of biomolecular complex structure predictions. A tool called DisVis, originally developed for mass spectrometry data, is investigated for its potential to improve the precision of co-evolution predicted contacts. Results show that integrating DisVis with docking software HADDOCK can enhance the quality of docking predictions for low precision contact data.
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2023)
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
Chemistry, Multidisciplinary
Jessica Pihl, Thomas M. M. Clausen, Jiarong Zhou, Nishta Krishnan, Maj S. S. Orum-Madsen, Tobias Gustavsson, Robert Dagil, Mads Daugaard, Swati Choudhary, Camilla Foged, Jeffrey D. D. Esko, Liangfang Zhang, Ronnie H. H. Fang, Ali Salanti
Summary: Malaria-infected erythrocytes and oncofetal CS have distinct tropism and can potentially be used for cancer targeting. Researchers have developed a drug delivery platform using erythrocyte membrane-coated nanoparticles that mimic malaria-infected erythrocytes and specifically target and kill melanoma cells. This biomimetic approach shows potential as a broadly targeted cancer therapy.
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.
Correction
Multidisciplinary Sciences
Andrea Sottini, Alessandro Borgia, Madeleine B. Borgia, Katrine Bugge, Daniel Nettels, Aritra Chowdhury, Petur O. Heidarsson, Franziska Zosel, Robert B. Best, Birthe B. Kragelund, Benjamin Schuler
NATURE COMMUNICATIONS
(2023)
Article
Biology
Felix van der Krift, Dick W. Zijlmans, Rhythm Shukla, Ali Javed, Panagiotis Koukos, Laura L. E. Schwarz, Elpetra P. M. Timmermans-Sprang, Peter E. M. Maas, Digvijay Gahtory, Maurits van den Nieuwboer, Jan A. Mol, Ger J. Strous, Alexandre M. J. J. Bonvin, Mario van der Stelt, Edwin J. A. Veldhuizen, Markus Weingarth, Michiel Vermeulen, Judith Klumperman, Madelon M. Maurice
Summary: Cancer cells rely heavily on the folate cycle for their metabolic needs, but chemotherapy drugs like methotrexate and 5-fluorouracil disrupt this cycle. However, therapy-induced resistance is a problem, and the lack of FPGS is associated with resistance to these drugs. The development of alternative antifolate drugs can selectively target FPGS-deficient cells during chemotherapy, taking advantage of their vulnerability.
LIFE SCIENCE ALLIANCE
(2023)
Article
Biochemical Research Methods
Manon Reau, Nicolas Renaud, Li C. Xue, Alexandre M. J. J. Bonvin
Summary: DeepRank-GNN is a modular and customizable deep-learning framework that converts protein-protein interfaces into graphs for problem-specific interaction pattern learning. It demonstrates competitive performance in scoring docking poses and discriminating biological and crystal interfaces, with significant improvements in speed and storage requirement compared to DeepRank.
Review
Cell Biology
Alex S. Holehouse, Birthe B. Kragelund
Summary: Intrinsically disordered protein regions, lacking a stable 3D structure, are structurally heterogeneous and widely present in all kingdoms of life. Despite their lack of a defined structure, these regions play essential roles in cellular processes and can be regulated by their structural and chemical context. Recent studies have advanced our understanding of the link between protein sequence and conformational behavior in disordered regions, but the connection between sequence and molecular function is still not well defined.
NATURE REVIEWS MOLECULAR CELL BIOLOGY
(2023)