Article
Multidisciplinary Sciences
Amin Addetia, Luca Piccoli, James Brett Case, Young-Jun Park, Martina Beltramello, Barbara Guarino, Ha Dang, Guilherme Dias de Melo, Dora Pinto, Kaitlin Sprouse, Suzanne M. Scheaffer, Jessica Bassi, Chiara Silacci-Fregni, Francesco Muoio, Marco Dini, Lucia Vincenzetti, Rima Acosta, Daisy Johnson, Sambhavi Subramanian, Christian Saliba, Martina Giurdanella, Gloria Lombardo, Giada Leoni, Katja Culap, Carley Mcalister, Anushka Rajesh, Exequiel Dellota, Jiayi Zhou, Nisar Farhat, Dana Bohan, Julia Noack, Alex Chen, Florian A. Lempp, Joel Quispe, Lauriane Kergoat, Florence Larrous, Elisabetta Cameroni, Bradley Whitener, Olivier Giannini, Pietro Cippa, Alessandro Ceschi, Paolo Ferrari, Alessandra Franzetti-Pellanda, Maira Biggiogero, Christian Garzoni, Stephanie Zappi, Luca Bernasconi, Min Jeong Kim, Laura E. Rosen, Gretja Schnell, Nadine Czudnochowski, Fabio Benigni, Nicholas Franko, Jennifer K. Logue, Courtney Yoshiyama, Cameron Stewart, Helen Chu, Herve Bourhy, Michael A. Schmid, Lisa A. Purcell, Gyorgy Snell, Antonio Lanzavecchia, Michael S. Diamond, Davide Corti, David Veesler
Summary: The recently emerged BQ.1.1 and XBB.1.5 variants of SARS-CoV-2 have a higher affinity for the host ACE2 receptor and more efficiently promote fusion with host cell membranes compared to earlier Omicron variants. Although the neutralizing activity is reduced, vaccine-induced human plasma antibodies still cross-react with and trigger effector functions against current Omicron variants, providing a mechanism of protection against disease.
Article
Biophysics
Taro Saito, Yutaka Shimizu, Kaori Tsukakoshi, Koichi Abe, Jinhee Lee, Kinuko Ueno, Ryutaro Asano, Brian Jones, Tomohiro Yamada, Tatsuki Nakano, Jiaxing Tong, Asami Hishiki, Kodai Hara, Hiroshi Hashimoto, Koji Sode, Toshimasa Toyo'oka, Kenichiro Todoroki, Kazunori Ikebukuro
Summary: A novel anti-idiotype aptamer A14#1 with extraordinary specificity against the anti-vascular endothelial growth factor therapeutic mAb, bevacizumab, was developed. The affinity of A14#1 to bevacizumab markedly increased at pH 4.7, enabling it to be potentially useful for therapeutic drug measurement as a novel ligand of bevacizumab.
BIOSENSORS & BIOELECTRONICS
(2022)
Review
Oncology
Heidi M. Haikala, Pasi A. Janne
Summary: HER3, a pseudokinase member of the EGFR family, plays a crucial role in tumor progression and drug resistance. Despite being discovered over 30 years ago, therapeutic interventions targeting HER3 have not yet received clinical approval, leading to increasing preclinical and clinical trials.
CLINICAL CANCER RESEARCH
(2021)
Article
Cell Biology
Marcia R. Campbell, Ana Ruiz-Saenz, Yuntian Zhang, Elliott Peterson, Veronica Steri, Julie Oeffinger, Maryjo Sampang, Natalia Jura, Mark M. Moasser
Summary: This article presents an extensive structure-function analysis of HER2 and HER3 signaling in cancer treatment. It reveals that the extracellular domains (ECDs) of these receptors are not essential for tumorigenic signaling and their conformational changes do not affect the dimerization interface. Additionally, disruptive receptor engineering fails to disturb tumorigenic signaling. The overexpression of HER2 uncouples intracellular signaling from extracellular constraints.
Review
Gastroenterology & Hepatology
Herbert Tilg, Timon E. Adolph, Frank Tacke
Summary: Inflammation plays a significant role in the progression of liver diseases such as hepatitis, NAFLD, and alcohol-related liver disease. Studies have shown that cytokines and cellular stress sensors contribute to disease processes in the liver. Unresolved inflammation and liver injury can lead to scarring, fibrosis, and cirrhosis, and may progress to liver cancer. Strategies to reduce inflammation in immune-mediated conditions have been widely used, but there is emerging evidence for immunomodulatory therapies in liver diseases.
Article
Oncology
Igor Odintsov, Allan J. W. Lui, Whitney J. Sisso, Eric Gladstone, Zebing Liu, Lukas Delasos, Renate I. Kurth, Exequiel M. Sisso, Morana Vojnic, Inna Khodos, Marissa S. Mattar, Elisa de Stanchina, Shawn M. Leland, Marc Ladanyi, Romel Somwar
Summary: The study demonstrates that the anti-HER3 antibody seribantumab inhibits NRG1 fusion-driven tumorigenesis in breast, lung, and ovarian cancer models, inducing apoptosis and blocking activation of ERBB family members and downstream signaling pathways. Seribantumab shows promising therapeutic potential for NRG1-rearranged cancers.
CLINICAL CANCER RESEARCH
(2021)
Article
Cell Biology
J. M. Vicencio, R. Evans, R. Green, Z. An, J. Deng, C. Treacy, R. Mustapha, J. Monypenny, C. Costoya, K. Lawler, K. Ng, K. De-Souza, O. Coban, V Gomez, J. Clancy, S. H. Chen, A. Chalk, F. Wong, P. Gordon, C. Savage, C. Gomes, T. Pan, G. Alfano, L. Dolcetti, J. N. E. Chan, F. Flores-Borja, P. R. Barber, G. Weitsman, D. Sosnowska, E. Capone, S. Iacobelli, D. Hochhauser, J. A. Hartley, M. Parsons, J. N. Arnold, S. Ameer-Beg, S. A. Quezada, Y. Yarden, G. Sala, T. Ng
Summary: In this study, the combination of osimertinib and anti-HER3 monoclonal antibodies was explored, and it was found that the immune system played a role in eliminating lung cancer cells by regulating the cGAS-STING pathway and innate immunity.
CELL DEATH & DISEASE
(2022)
Article
Multidisciplinary Sciences
Ian Wilkinson, Stephen Anderson, Jeremy Fry, Louis Alex Julien, David Neville, Omar Qureshi, Gary Watts, Geoff Hale
Summary: Novel variants with specific amino acid substitutions at L234 and L235 combined with G236R substitution completely eliminate binding to Fc. receptors, avoiding inflammatory responses and improving the safety and efficacy of therapeutic antibodies and Fc fusion proteins.
Article
Oncology
Amrita Basu, Gabriella K. Albert, Sabrina Awshah, Jashodeep Datta, Krithika N. Kodumudi, Corey Gallen, Amber Beyer, Keiran S. M. Smalley, Paulo C. Rodriguez, Derek R. Duckett, Peter A. Forsyth, Aixa Soyano, Gary K. Koski, Ricardo Lima Barros Costa, Heather Han, Hatem Soliman, Marie Catherine Lee, Pawel Kalinski, Brian J. Czerniecki
Summary: This study identifies immunogenic MHC class II-binding HER3 peptides that elicit HER3-specific CD4(+) Th1 responses, suggesting their potential application in immunotherapies for HER3-overexpressing tumors.
CANCER IMMUNOLOGY RESEARCH
(2022)
Article
Microbiology
Ming-Yu Wang, Jun-Bin Chen, Rui Wu, Hai-Long Guo, Yan Chen, Zhen-Ju Li, Lu-Yang Wei, Chuang Liu, Sheng-Feng He, Mei-Da Du, Ya-long Guo, You-Liang Peng, Jonathan D. G. Jones, Detlef Weigel, Jian-Hua Huang, Wang-Sheng Zhu
Summary: This study reveals that the Pseudomonas syringae effector AvrPtoB can suppress cell death mediated by ADR1-L1 and ADR1-L2, but ADR1 evades this suppression by diversifying. In addition, the intracellular sensor SNC1 interacts with the CCR domains of ADR1-L1/L2, triggering immune responses.
CELL HOST & MICROBE
(2023)
Article
Nutrition & Dietetics
Konstantinos Christofyllakis, Frank Neumann, Moritz Bewarder, Lorenz Thurner, Dominic Kaddu-Mulindwa, Igor Age Kos, Vadim Lesan, Joerg Thomas Bittenbring
Summary: Patients with diffuse large cell lymphoma and sufficient vitamin D supply benefit more from immuno-chemotherapy with rituximab, especially female patients. Vitamin D increases the ADCC of NK cells in a sex-dependent manner, but the mechanism of how it enhances NK cell efficiency is unclear.
Article
Immunology
Wissam Charab, Matthew G. Rosenberger, Haridha Shivram, Justin M. Mirazee, Moses Donkor, Soumya R. Shekhar, Donjeta Gjuka, Kimberly H. Khoo, Jin Eyun Kim, Vishwanath R. Iyer, George Georgiou
Summary: Elevated levels of circulating immune complexes are associated with autoimmunity and worse prognoses in cancer. IgG-ICs inhibit the proliferation and differentiation of a subset of naive T cells while stimulating the division of another naive-like T cell subset. Phenotypic analysis revealed immature features in the inhibited T cell subset and transcriptional features indicative of a more differentiated phenotype in the stimulated T cell subset.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Oncology
Hui Lyu, Fei Shen, Sanbao Ruan, Congcong Tan, Jundong Zhou, Ann D. Thor, Bolin Liu
Summary: Increased expression of HER3 is associated with poor prognosis in TNBC. Inhibition of HER3 expression inhibits TNBC cell proliferation and tumor growth. The anti-HER3 monoclonal antibody (mAb) 4A7 enhances the efficacy of gefitinib or paclitaxel in TNBC.
CANCER CELL INTERNATIONAL
(2023)
Article
Biochemistry & Molecular Biology
Haiming Dai, Kevin L. Peterson, Karen S. Flatten, X. Wei Meng, Annapoorna Venkatachalam, Cristina Correia, Marina Ramirez-Alvarado, Yuan-Ping Pang, Scott H. Kaufmann
Summary: This study investigated the structure and function of BAK subdomains using molecular dynamics simulations, surface plasmon resonance, and various assays. The results indicate that the helical regions alpha 5 and alpha 6 of BAK bind to the lipid cardiolipin in the mitochondrial outer membrane. Tandem peptides corresponding to these helical regions can induce mitochondrial outer membrane permeabilization (MOMP) in the absence of the rest of the BAK protein by localizing exogenous proteins to mitochondria and permeabilizing liposomes composed of MOM lipids.
CELL DEATH AND DIFFERENTIATION
(2023)
Review
Immunology
Birte Ohm, Wolfgang Jungraithmayr
Summary: This review article discusses the role of B cells in lung transplantation rejection, indicating that certain subsets of B cells can promote immune tolerance and highlighting the prospects of using B cell-targeted therapies.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
K. Stakyte, M. Rotheneder, K. Lammens, J. D. Bartho, U. Graedler, T. Fuchss, U. Pehl, A. Alt, E. van de Logt, K. P. Hopfner
Summary: High-resolution cryo-EM structures of human ATM bound to ATP gamma S and two distinct ATM inhibitors provide insights into the mechanism of inhibitor selectivity and offer a framework for structure-based drug design. The mode of action and selectivity of the ATM inhibitors can be explained by structural comparison and provide a framework for structure-based drug design.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Adrian M. Bandera, Joseph Bartho, Katja Lammens, David Jan Drexler, Jasmin Kleinschwaerzer, Karl-Peter Hopfner, Gregor Witte
Summary: The cyclic dinucleotide second messenger c-di-AMP plays a crucial role in regulating potassium homeostasis and osmolyte transport in bacteria by interacting with proteins and transcription factors to alter cellular processes. BusR, a member of the GntR family of transcription factors, downregulates gene transcription of BusA transporter upon c-di-AMP binding. Structural and biochemical characterization of BusR reveals a unique domain assembly allowing recognition of a specific binding motif, leading to transcriptional repression.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Simon Veth, Adrian Fuchs, Dilara Oezdemir, Clemens Dialer, David Jan Drexler, Fabian Knechtel, Gregor Witte, Karl-Peter Hopfner, Thomas Carell, Evelyn Ploetz
Summary: The cGAS-STING pathway plays a crucial role in sensing cytosolic DNA. Research on the development of fluorescent moieties and synthesis of fluorescent molecules for detection is important for the therapeutic potential of this pathway.
Article
Biochemistry & Molecular Biology
Felix J. Metzner, Elisabeth Huber, Karl-Peter Hopfner, Katja Lammens
Summary: The Schlafen family, including SLFN5, plays important roles in cell cycle regulation, DNA repair, etc. The structure of SLFN5 differs from ATPase and can bind both tRNA and DNA, possibly involved in transcriptional regulation.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Chemistry, Multidisciplinary
Samuele Stazzoni, Daniel F. R. Bohmer, Fabian Hernichel, Dilara Oezdemir, Aikaterini Pappa, David Drexler, Stefan Bauernfried, Gregor Witte, Mirko Wagner, Simon Veth, Karl-Peter Hopfner, Veit Hornung, Lars M. Koenig, Thomas Carell
Summary: 2',3'-cGAMP is a second messenger formed during cellular recognition of foreign cytosolic DNA, binding to the adaptor protein STING to induce an immune response. Studies show that analogs lacking secondary ribose-OH groups can serve as poxin-resistant STING agonists, with dideoxy-2',3'-cAAMP showing high antitumor response in mice.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Immunology
Nina Kessler, Susanne F. Viehmann, Calvin Krollmann, Karola Mai, Katharina M. Kirschner, Hella Luksch, Prasanti Kotagiri, Alexander M. C. Boehner, Dennis Huugen, Carina C. de Oliveira Mann, Simon Otten, Stefanie A. Weiss, Thomas Zillinger, Kristiyana Dobrikova, Dieter E. Jenne, Rayk Behrendt, Andrea Ablasser, Eva Bartok, Gunther Hartmann, Karl-Peter Hopfner, Paul A. Lyons, Peter Boor, Angela Roesen-Wolff, Lino L. Teichmann, Peter Heeringa, Christian Kurts, Natalio Garbi
Summary: The study identifies abnormal DNA recognition and IFN-I production as drivers of severe ANCA-associated vasculitis, and demonstrates that blocking this pathway can ameliorate the disease and accelerate recovery, suggesting potential therapeutic targets for patients.
JOURNAL OF EXPERIMENTAL MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Fabian Gut, Lisa Kaeshammer, Katja Lammens, Joseph D. Bartho, Anna-Maria Boggusch, Erik van de Logt, Brigitte Kessler, Karl-Peter Hopfner
Summary: This study reveals the mechanism of action of the Mre11-Rad50 complex in DNA repair. The results show that Mre11-Rad50 bends internal DNA for endonucleolytic cleavage and processes internal DNA, DNA ends, and hairpins in a similar ATP-regulated conformational state.
Article
Multidisciplinary Sciences
Elham Khatamzas, Markus H. Antwerpen, Alexandra Rehn, Alexander Graf, Johannes Christian Hellmuth, Alexandra Hollaus, Anne-Wiebe Mohr, Erik Gaitzsch, Tobias Weiglein, Enrico Georgi, Clemens Scherer, Stephanie-Susanne Stecher, Stefanie Gruetzner, Helmut Blum, Stefan Krebs, Anna Reischer, Alexandra Leutbecher, Marion Subklewe, Andrea Dick, Sabine Zange, Philipp Girl, Katharina Mueller, Oliver Weigert, Karl-Peter Hopfner, Hans-Joachim Stemmler, Michael Von Bergwelt-Baildon, Oliver T. Keppler, Roman Woelfel, Maximilian Muenchhoff, Andreas Moosmann
Summary: This study reveals a potential association between SARS-CoV-2 mutations and CD8 T cell alterations, suggesting the involvement of CD8 T cells in the evasion of SARS-CoV-2 from host immunity.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Felix J. Metzner, Simon J. Wenzl, Michael Kugler, Stefan Krebs, Karl-Peter Hopfner, Katja Lammens
Summary: This study utilizes cryoelectron microscopy and biochemical assays to investigate the tRNA endoribonuclease and DNA binding functions of human Schlafen 11 (SLFN11). The findings provide detailed insights into the mechanism of SLFN11's endoribonuclease activity and its potential role in blocking stressed replication forks. Understanding these functions is important for understanding the antiviral and predictive biomarker roles of SLFN11 in cancer.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Markus Matthias Hohle, Katja Lammens, Fabian Gut, Bingzhi Wang, Sophia Kahler, Kathrin Kugler, Michael Till, Roland Beckmann, Karl-Peter Hopfner, Christophe Jung
Summary: This study presents a method to assess the vitreous ice layer thickness of sample coated grids, using an optical interferometric microscope and image analysis software based on artificial neural networks for unbiased sample selection. Experiments demonstrate that this method performs well for different protein complexes and grid types, providing a fast assessment of ice quality.
SCIENTIFIC REPORTS
(2022)
Meeting Abstract
Hematology
Maryam Kazerani, Lucas Wange, Benjamin Tast, Maria Solovey, Daniel Nixdorf, Lisa Rohrbacher, Christina Heitmueller, Thomas Koehnke, Frauke Schnorfeil, Victoria V. Grunwald, Karsten Spiekermann, Klaus H. Metzeler, Karl-Peter Hopfner, Wolfgang Enard, Veit L. Buecklein, Marion Subklewe
Correction
Immunology
Nina Kessler, Susanne F. Viehmann, Calvin Krollmann, Karola Mai, Katharina M. Kirschner, Hella Luksch, Prasanti Kotagiri, Alexander M. C. Boehner, Dennis Huugen, Carina C. de Oliveira Mann, Simon Otten, Stefanie A. I. Weiss, Thomas Zillinger, Kristiyana Dobrikova, Dieter E. Jenne, Rayk Behrendt, Andrea Ablasser, Eva Bartok, Gunther Hartmann, Karl-Peter Hopfner, Paul A. Lyons, Peter Boor, Angela Roesen-Wolff, Lino L. Teichmann, Peter Heeringa, Christian Kurts, Natalio Garbi
JOURNAL OF EXPERIMENTAL MEDICINE
(2022)
Article
Multidisciplinary Sciences
Franziska Kunert, Felix J. Metzner, James Jung, Markus Hoepfler, Stephan Woike, Kevin Schall, Dirk Kostrewa, Manuela Moldt, Jia-Xuan Chen, Susanne Bantele, Boris Pfander, Sebastian Eustermann, Karl-Peter Hopfner
Summary: The nucleosomal landscape of chromatin is influenced by the chromatin remodeler INO80, which moves nucleosomes to the boundary of gene regulatory elements through ATP-dependent nucleosome sliding activity regulated by extranucleosomal DNA features. Cryo-electron microscopy and functional assays were used to investigate how INO80 binds and is regulated by extranucleosomal DNA. The study revealed the mechanism of linker DNA binding and provided insights into the recruitment of YY1/Ies4 subunits as well as the architectural similarities between INO80 and SWI/SNF complexes.
Review
Biochemistry & Molecular Biology
Karl-Peter Hopfner
Summary: The Mre11-Rad50-(Nbs1/Xrs2) complex is a conserved factor that repairs DNA double-strand breaks and other DNA termini in all species. It functions as a complex DNA-associated molecular machine that cuts various types of free and obstructed DNA termini for repair, while leaving undamaged DNA intact. Recent studies have revealed the mechanisms of DNA end recognition, endo/exonuclease activities, nuclease regulation, and DNA scaffolding in the Mre11-Rad50 orthologs. This review summarizes our current understanding and recent progress on the functional architecture of Mre11-Rad50 and how it acts as a DNA topology-specific endo/exonuclease.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2023)
Article
Biochemistry & Molecular Biology
Stephan Woike, Sebastian Eustermann, James Jung, Simon Josef Wenzl, Goetz Hagemann, Joseph Bartho, Katja Lammens, Agata Butryn, Franz Herzog, Karl-Peter Hopfner
Summary: The Swi2/Snf2 family transcription regulator Mot1 utilizes ATP to remove the TBP from promoters and reposition it on DNA. Cryo-EM structures reveal that Mot1 dissociates TBP without tracking DNA grooves, instead gripping DNA in the presence of ATP and moving TBP to a less stable position. The displaced TBP is then trapped by a chaperone element. Mechanistic similarities are observed with RNA gripping helicases and immune sensors.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2023)