Article
Virology
Franziska Rothemund, Myriam Scherer, Eva-Maria Schilling, Johannes Schweininger, Yves A. Muller, Thomas Stamminger
Summary: The study analyzed the functions of human cytomegalovirus (CMV) immediate early 1 (IE1) protein and rat CMV IE1 (rIE1) protein, and found that their interactions with cellular proteins PML and FEN1 were species-specific. It was also discovered that both IE1 proteins can antagonize human STAT2, but different regions of the viral proteins were involved in the interaction. Additionally, the study revealed that the binding of PML, FEN1, and STAT2 was conserved between primate and rodent proteins, but rIE1 lacked chromatin tethering function.
Article
Multidisciplinary Sciences
Andreja Majerle, San Hadzi, Jana Aupic, Tadej Satler, Fabio Lapenta, Ziga Strmsek, Jurij Lah, Remy Loris, Roman Jerala
Summary: The study discusses the use of single-chain camelid antibodies to target various CC modules in protein origami designs, showing that these nanobodies can recognize the same CC modules in different polyhedral contexts. This expands the versatility of protein origami scaffolds, allowing for functionalization of polyhedra with nanobodies in desired stoichiometry. Crystal structures and small-angle X-ray scattering reveal binding interactions between nanobodies and CC dimers in designed protein structures, providing opportunities for functionalizing CC protein origami polyhedra or bionanomaterials.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Leon Harrington, Jordan M. Fletcher, Tamara Heermann, Derek N. Woolfson, Petra Schwille
Summary: The article presents a peptide-based molecular switch that regulates dimer formation and lipid membrane targeting via reversible phosphorylation, with potential applications in introducing dynamic processes into synthetic biological systems.
NATURE COMMUNICATIONS
(2021)
Article
Engineering, Biomedical
Marcos Gil-Garcia, Salvador Ventura
Summary: The study presents a novel approach to create highly functional, non-amyloid, and fluorescent inclusion bodies (IBs) using natural coiled-coil self-assembly properties. These protein-based nanoparticles effectively capture antibodies and are utilized for specific and simultaneous targeting of two unrelated cell types, potentially valuable in bioimaging and immunotherapy applications.
ACTA BIOMATERIALIA
(2021)
Article
Chemistry, Medicinal
Huan Wang, Xinling Wang, Jiahui Li, Qing Li, Siliang Feng, Lu Lu, Chao Wang, Shibo Jiang
Summary: Both the deep pocket region and its neighboring subpocket site on the N-trimer of HIV-1 gp41 protein can be targeted for the development of HIV-1 entry inhibitors. This study reports the design of alpha-helical lipopeptides with non-native protein sequences as highly active HIV-1 fusion inhibitors that can occupy both the deep pocket and subpocket sites.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Respiratory System
Amelia Shoemark, Helen Griffin, Gabrielle Wheway, Claire Hogg, Jane S. Lucas, Genomics England Research Genomics England Res Consortium, Carme Camps, Jenny Taylor, Mary Carroll, Michael R. Loebinger, James D. Chalmers, Deborah Morris-Rosendahl, Hannah M. Mitchison, Anthony De Soyza
Summary: This study suggests that motile ciliopathies are often underdiagnosed as a cause of bronchiectasis. Increased utilization of genetic testing can help identify bronchiectasis caused by motile ciliopathies and ensure appropriate management.
EUROPEAN RESPIRATORY JOURNAL
(2022)
Review
Biochemistry & Molecular Biology
Sergey A. Silonov, Eugene Y. Smirnov, Irina M. Kuznetsova, Konstantin K. Turoverov, Alexander V. Fonin
Summary: In this review, the recent progress in understanding the role of individual domains of PML protein, its post-translational modifications, and polyvalent nonspecific interactions in the formation of PML bodies is highlighted. A new hypothetical model of PML body formation is proposed based on the available literature.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Engineering, Biomedical
Romane Oliverio, Victor Patenaude, Benoit Liberelle, Nick Virgilio, Xavier Banquy, Gregory De Crescenzo
Summary: This research presents a highly tunable platform for the capture and sustained delivery of growth factors using affinity peptides in macroporous, fully interconnected dextran hydrogels. It addresses several ongoing challenges by providing a versatile platform for the delivery of a wide range of stable, bioactive molecules; a passive, affinity-based loading of growth factors in the platform, paving the way for in situ (re)loading of the device; and four different control parameters to finely tune growth factor capture and release. Overall, our macroporous dextran hydrogels have vast potential for applications in controlled delivery, tissue engineering, and regenerative medicine.
ACTA BIOMATERIALIA
(2022)
Article
Microbiology
Peter S. Back, Andy S. Moon, Rebecca R. Pasquarelli, Hannah N. Bell, Juan A. Torres, Allan L. Chen, Jihui Sha, Ajay A. Vashisht, James A. Wohlschlegel, Peter J. Bradley, Jon P. Boyle
Summary: This study demonstrates the important role of IMC29 protein in parasite replication and identifies several IMC proteins involved in the early stages of replication. These findings contribute to our understanding of the function and replication mechanism of this organelle.
Article
Chemistry, Physical
J. Karl Spinti, Fernando Neiva Nunes, Manuel N. Melo
Summary: The Martini 3 coarse-grain force field has significantly improved compared to its previous version. This study evaluates the accuracy of Martini 2 and 3 in protein interactions in two different systems: coiled coil peptide dimers and transmembrane peptides. Martini 2 incorrectly forms coiled coil dimers, while Martini 3 does it correctly. In terms of transmembrane peptides, Martini 3 better represents the relationship between membrane thickness and peptide tilt, but shorter peptides do not remain transmembrane. Mitigation strategies involving scaling interactions or restraining the system are discussed.
CHEMICAL PHYSICS LETTERS
(2023)
Article
Microbiology
Eva-Maria Schilling, Myriam Scherer, Franziska Rothemund, Thomas Stamminger
Summary: FEN1 plays a critical role in viral infections, especially in HCMV infection where IE1 can manipulate FEN1 to facilitate viral DNA replication. This discovery may lead to new antiviral therapeutic options to combat HCMV infections.
Article
Multidisciplinary Sciences
Maria Elias, Samar Gani, Yana Lerner, Katreen Yamin, Chen Tor, Adarsh Patel, Avi Matityahu, Moshe Dessau, Nir Qvit, Itay Onn
Summary: This study reports on the development of the first cohesin-inhibiting peptide (CIP) that can inhibit the function of cohesin in cells, and discusses the potential application of CIPs as a therapeutic approach.
Article
Plant Sciences
Hye-Young Lee, Hyunggon Mang, Eunhye Choi, Ye-Eun Seo, Myung-Shin Kim, Soohyun Oh, Saet-Byul Kim, Doil Choi
Summary: This study identified a group of NLRs (ANLs) carrying autoactive coiled-coil domains in pepper plants, which may function as singleton NLRs. The research also revealed that autoactive coiled-coil domains are well conserved in Solanaceae plants and rice, a monocot plant. Furthermore, phylogenetic analyses showed that ANLs are present in all tested seed plants.
Article
Multidisciplinary Sciences
Yosuke Ito, Yasuhisa Terao, Shohei Noma, Michihira Tagami, Emiko Yoshida, Yoshihide Hayashizaki, Masayoshi Itoh, Hideya Kawaji
Summary: Gene expression regulation includes transcriptional and post-transcriptional control. Research has shown the involvement of the TACC2 gene in tumors, with the activity of the intronic promoter p10 linked to lymph node metastasis in low-risk endometrial cancer patients. Analysis of intronic promoter-derived isoforms revealed numerous exons contributing to isoform diversity, indicating complex post-transcriptional processes at the TACC2 locus in both cancer and normal cells.
SCIENTIFIC REPORTS
(2021)
Review
Biochemical Research Methods
Christopher J. Addonizio, Brant D. Gates, Matthew J. Webber
Summary: The fields of precision imaging and drug delivery have introduced various tools to enhance target specificity and efficacy in diagnosing and treating diseases. Biological molecules and molecular recognition motifs play key roles in ensuring active targeting and specificity, while bioorthogonal covalent conjugations and supramolecular motifs offer possibilities for in situ complexation under physiological conditions.
BIOCONJUGATE CHEMISTRY
(2021)
Article
Biology
Myriam Scherer, Clarissa Read, Gregor Neusser, Christine Kranz, Anna K. Kuderna, Regina Mueller, Florian Full, Sonja Woerz, Anna Reichel, Eva-Maria Schilling, Paul Walther, Thomas Stamminger
Summary: PML nuclear bodies undergo rearrangement to form giant cages upon viral infection, trapping viral genomes and capsids, and providing a multilayered defense strategy against viral infections.
Article
Biochemistry & Molecular Biology
Lucas Weissenborn, Elie Richel, Helena Hueseman, Julia Welzer, Silvan Beck, Simon Schaefer, Heinrich Sticht, Klaus Ueberla, Jutta Eichler
Summary: Using the structure of a de novo designed miniprotein (LCB1) in complex with the receptor binding domain (RBD) of the SARS-CoV-2 spike protein, truncated peptide variants of LCB1 were generated and characterized. These variants, which retained virus neutralizing potency against different SARS-CoV-2 variants of concern (VOC), showed even stronger antiviral activity than the full-length peptide. The cyclic variant of the two-helix peptides exhibited significantly improved proteolytic stability, making it a better candidate for SARS-CoV-2 therapy. These peptides can also be chemically modified to further stabilize them against degradation and enhance their virus neutralizing capacity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Virology
Franziska Rothemund, Myriam Scherer, Eva-Maria Schilling, Johannes Schweininger, Yves A. Muller, Thomas Stamminger
Summary: The study analyzed the functions of human cytomegalovirus (CMV) immediate early 1 (IE1) protein and rat CMV IE1 (rIE1) protein, and found that their interactions with cellular proteins PML and FEN1 were species-specific. It was also discovered that both IE1 proteins can antagonize human STAT2, but different regions of the viral proteins were involved in the interaction. Additionally, the study revealed that the binding of PML, FEN1, and STAT2 was conserved between primate and rodent proteins, but rIE1 lacked chromatin tethering function.
Article
Microbiology
Anne-Charlotte Stilp, Myriam Scherer, Patrick Koenig, Axel Fuerstberger, Hans A. Kestler, Thomas Stamminger
Summary: In this study, it was discovered that the chromatin remodeling factor ATRX has a co-activating role in innate immunity, regulating chromatin accessibility and transcription of interferons and interferon-stimulated genes. It affects the antiviral immune response by decreasing transcription and secretion of type I interferons, leading to reduced expression of interferon-stimulated genes.
Article
Clinical Neurology
Konrad Platzer, Heinrich Sticht, Caleb Bupp, Mythily Ganapathi, Elaine M. Pereira, Gwenael Le Guyader, Frederic Bilan, Lindsay B. Henderson, Johannes R. Lemke, Holger Taschenberger, Nils Brose, Rami Abou Jamra, Sonja M. Wojcik
Summary: This study identifies de novo missense variants in the SLC32A1 gene as a novel cause of developmental and epileptic encephalopathy. These variants may impair GABAergic neurotransmission through altered synaptic vesicle filling and synaptic short-term plasticity.
ANNALS OF NEUROLOGY
(2022)
Article
Biochemistry & Molecular Biology
Johannes Luppe, Heinrich Sticht, Francois Lecoquierre, Alice Goldenberg, Kathleen M. Gorman, Ben Molloy, Emanuele Agolini, Antonio Novelli, Silvana Briuglia, Outi Kuismin, Carlo Marcelis, Antonio Vitobello, Anne-Sophie Denomme-Pichon, Sophie Julia, Johannes R. Lemke, Rami Abou Jamra, Konrad Platzer
Summary: The study identified eight individuals with ultra rare variants in STX1A who presented with a spectrum of intellectual disability, autism, and epilepsy. The phenotypic course varied depending on the type of variant, with missense variants mainly causing epilepsy and single amino acid deletions and the splice variant causing intellectual disability and autistic behavior. In silico modeling showed different impaired protein-protein interactions for missense variants and single amino acid deletions. These findings suggest two different pathogenic mechanisms underlying STX1A-related neurodevelopmental disorders.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Biochemistry & Molecular Biology
Ella Vintschger, Dennis Kraemer, Pascal Joset, Anselm H. C. Horn, Anita Rauch, Heinrich Sticht, Ruxandra Bachmann-Gagescu
Summary: Next generation sequencing (NGS) is used to detect carrier status for rare recessive disorders. The recent ACMG recommendations support NGS-based carrier screening (NGS-CS) for genes with a carrier frequency > 1/200. However, variant interpretation in healthy individuals presents challenges, and the true carrier frequencies are uncertain. Thus, genetic counseling for NGS-CS should disclose these limitations.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Engineering, Electrical & Electronic
Lukas Brand, Moritz Garkisch, Sebastian Lotter, Maximilian Schafer, Andreas Burkovski, Heinrich Sticht, Kathrin Castiglione, Robert Schober
Summary: In this paper, the concept of media modulation based molecular communication (MC) is proposed, where the transmitter (TX) is placed outside the channel and utilizes signaling molecules already present inside the system. The usage of photochromic molecules for media modulation is studied, and a statistical model and maximum likelihood detector are developed to analyze the reliability of information transmission.
IEEE TRANSACTIONS ON COMMUNICATIONS
(2022)
Article
Cell Biology
Josephine Loesing, Sigrun Haege, Martin Schuetz, Sabrina Wagner, Julia Wardin, Heinrich Sticht, Manfred Marschall
Summary: Herpesviruses replicate their genomes and assemble their capsids in the host cell nucleus. To progress towards morphogenesis in the cytoplasm, herpesviruses evolved the strategy of nuclear egress as a highly regulated process of nucleo-cytoplasmic capsid transition. The study identified cross-viral interactions in the formation of the nuclear egress complex (NEC) and provided insights into potential targets for the development of NEC-directed inhibitory small molecules.
Article
Biochemistry & Molecular Biology
Paolo Zanoni, Katharina Steindl, Heinrich Sticht, Beatrice Oneda, Pascal Joset, Ivan Ivanovski, Anselm H. C. Horn, Elena. M. M. Cabello, Julia Laube, Markus Zweier, Alessandra Baumer, Anita Rauch, Nadia Khan
Summary: In this study, a comprehensive genetic and clinical analysis was conducted on a large cohort of pediatric MMA patients. RNF213 and neurofibromatosis type 1 (NF1) were identified as the two main subgroups. Patients with deleterious RNF213 variants exhibited severe clinical manifestations, early symptom onset, and a high rate of multiple territory strokes. NF1 patients had similar stroke burden compared to non-NF1 individuals and were often incidentally diagnosed during routine MRIs. The study also found that MMA-associated RNF213 variants had lower functional impact compared to those associated with aortic disease. The possible association of MMA with recurrent chromosomal imbalances and STAT3 deficiency was also discussed.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Biochemistry & Molecular Biology
Marcus Conrad, Anselm H. C. Horn, Heinrich Sticht
Summary: Through molecular dynamics simulations, it was found that the tautomers and charge states of histamine have a significant impact on its interaction with the histamine H1 receptor. The tau-tautomer formed stable interactions with the receptor, while the pi-tautomer only formed weaker hydrogen bonding interactions. Additionally, the dicationic histamine showed weaker interaction with the receptor and induced an inactive conformation in the absence of the G(q) protein. These findings have implications for the development of new ligands that stabilize specific activation states of the H1 receptor.
Article
Medicine, General & Internal
Una Ebong, Susanne Martina Buettner, Stefan A. Schmidt, Franziska Flack, Patrick Korf, Lynn Peters, Beate Gruener, Steffen Stenger, Thomas Stamminger, Hans Kestler, Meinrad Beer, Christopher Kloth
Summary: This study implemented an AI-based software prototype for the detection of COVID-19 pneumonia and differentiation between other types of pneumonia in lung CT datasets. The software achieved a sensitivity of 80.8% and a specificity of 50% for detecting COVID-19, but the human radiologist achieved a higher specificity of 97.2%.
Article
Biology
Manuel Deubler, Lucas Weissenborn, Simon Leukel, Anselm H. C. Horn, Jutta Eichler, Heinrich Sticht
Summary: PG16 is a broadly neutralizing antibody that binds to the gp120 subunit of the HIV-1 Env protein. Sulfation of Tyr100H in the CDRH3 residue enhances interactions with gp120 and stabilizes the protein-protein contacts and interactions with the gp120 glycan shield. PG16-CDRH3 can be used as a template to develop peptide mimetics as potential inhibitors of HIV invasion.
Article
Plant Sciences
Theresa Maria Reimann, Christina Muedsam, Christina Schachtler, Semra Ince, Heinrich Sticht, Christian Herrmann, Michael Stuerzl, Benedikt Kost
Summary: In this study, the Arabidopsis GBP orthologue AtGBPL3 was identified as a crucial component in mitotic nuclear envelope reformation, nuclear morphogenesis, and transcriptional repression during interphase. AtGBPL3 preferentially accumulates at the nuclear envelope in mitotically active root tips and interacts with centromeric chromatin and lamina components, leading to transcriptional repression of pericentromeric chromatin. Reduced expression of AtGBPL3 or associated lamina components results in altered nuclear morphology and overlapping transcriptional deregulation.
Article
Biochemistry & Molecular Biology
Sven Seitz, Anna Theresa Heusel, Thomas Stamminger, Myriam Scherer
Summary: PML nuclear bodies (PML-NBs) play a cell type-specific antiviral role against HCMV infection, with PML and Daxx having contrasting effects at different stages.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)