Explanipedia

Quantitative modeling of P-TEFb mediated CTD phosphorylation identifies local cooperativity Open

Domagoj Dorešić, Robert Düster, Vanessa Nakonecnij, Erika Dudkin, Matthias Geyer · 2025

Fine-tuned regulation of RNA polymerase II (Pol II) activity is essential for accurate gene expression. A key layer of this regulation involves phosphorylation of Pol II’s C-terminal domain (CTD), a repetitive heptapeptide tail that coordi…

Discovery of potent and selective inhibitors of human NLRP3 with a novel mechanism of action Open

Kevin Wilhelmsen, Aditi Deshpande, Sarah U. Tronnes, Maitriyee Mahanta, MATTHEW BANICKI , et al. · 2025

The NLRP3 inflammasome is an intracellular protein complex that causes inflammation via the release of IL-1β and pyroptosis. NLRP3 activation is associated with many age-related inflammatory diseases, and NLRP3 inhibition is a promising th…

A CDK11-dependent RNA polymerase II pause-checkpoint precedes CDK9-mediated transition to transcriptional elongation Open

Jennifer R. Devlin, Ben P. Martin, Nenad Bartoniček, Keziah Ting, Zheng Fan , et al. · 2025

Controlled gene expression is achieved through the intricate regulation of RNA polymerase II (Pol II) progression through transcription-cycle checkpoints. While the contribution of CDK9 for Pol II pause-release is well established, the req…

Targeted histone deacetylase degradation via chemical induced proximity by direct recruitment of the CUL4 complex adaptor protein DDB1 Open

Shiyang Zhai, Nicola Willemsen, Tao Sun, Mateo Malenica, Shixin Deng , et al. · 2025

Targeted protein degradation using proteolysis-targeting chimeras (PROTACs) has emerged as a powerful strategy for disease treatment. By recruiting E3 ligases, these molecules enable selective degradation of pathogenic proteins. Cereblon (…

Haploinsufficiency of ABL1 is associated with dominant isolated omphalocele Open

Caroline M. Kolvenbach, Öznur Yılmaz, Filipa M. Lopes, Jeshurun C. Kalanithy, Katharina Lemberg , et al. · 2025

Omphalocele is a rare birth defect of the abdominal wall that results in herniation of the visceral organs through the umbilicus. To date, there are no identified genetic causes for non-syndromic isolated omphalocele. Exome sequencing in a…

Inhibition of NLRP3 by a CNS-penetrating indazole scaffold Open

Jane Torp, Dominic Ferber, Hannes Buthmann, Gregor Hagelueken, Aditi Deshpande , et al. · 2025

Low-grade inflammation is a hallmark of ageing and a key cause of age-related impairments and diseases 1 . The NOD-like receptor NLRP3 senses a variety of danger signals and environmental insults, resulting in pro-inflammatory response, in…

Satb1 directs the differentiation of TH17 cells through suppression of IL-2 expression Open

Maren Köhne, Mehrnoush Hadaddzadeh Shakiba, Lisa Schmidleithner, Eva C. Schulte, Rebekka Scholz , et al. · 2025

T helper (T_H)17 cells are crucial for host defense in barrier organs, and their altered functionality can disrupt tissue homeostasis, increasing the risk of autoimmune diseases. Thus, it is essential to understand the mechanisms…

The inflammasome sensor NLRP3 interacts with REV7 to maintain genome integrity through homologous recombination Open

Delphine Burlet, Md Muntaz Khan, Sabine Hacot, Hannes Buthmann, Léa Bardoulet , et al. · 2025

DNA double-strand break (DSB) is a highly toxic lesion that can generate genome instability, a major source of tumorigenesis. DSBs are mainly repaired by non-homologous end joining (NHEJ) or homologous recombination (HR). The selection of …

Clustering of NLRP3 induced by membrane or protein scaffolds promotes inflammasome assembly Open

Elvira Boršić, Taja Železnik Ramuta, Sara Orehek, Mateja Erdani Kreft, Matthias Geyer , et al. · 2025

Development of AI-designed protein binders for detection and targeting of cancer cell surface proteins Open

Bianca Broske, Sophie C. Binder, Benjamin A. McEnroe, Tim Kempchen, Caroline I. Fandrey , et al. · 2025

Artificial intelligence (AI)-based protein design opens new avenues for the rapid generation of new research tools and therapeutics, but experimental validation lags behind the computational design throughput. Here, we present a scalable w…

Mechanisms of NLRP3 activation and inhibition elucidated by functional analysis of disease-associated variants Open

Shouya Feng, Matthew C Wierzbowski, Katja Hrovat-Schaale, Andreas Dumortier, Yaoyuan Zhang , et al. · 2025

Discovery of a Potent and Selective Inhibitor of Human NLRP3 with a Novel Binding Modality and Mechanism of Action Open

Kevin Wilhelmsen, Aditi Deshpande, Sarah U. Tronnes, Maitriyee Mahanta, MATTHEW BANICKI , et al. · 2024

The NLRP3 inflammasome is an intracellular protein complex that causes inflammation via the release of IL-1β and pyroptosis. NLRP3 activation is associated with many age-related inflammatory diseases, and NLRP3 inhibition is a promising th…

RNA-binding proteins hnRNPM and ELAVL1 promote type-I interferon induction downstream of the nucleic acid sensors cGAS and RIG-I Open

Alexander Kirchhoff, Anna‐Maria Herzner, Christian Urban, Antonio Piras, Robert Düster , et al. · 2024

Role of ZFHX4 in orofacial clefting based on human genetic data and zebrafish models Open

Nina Ishorst, Selina Hölzel, Carola Greve, Öznur Yılmaz, Tobias Lindenberg , et al. · 2024

Degrading the key component of the inflammasome: Development of an NLRP3 PROTAC Open

Tim Keuler, Dominic Ferber, Jonas Engelhardt, Christian Steinebach, Michael Marleaux , et al. · 2024

This study explores PROTACs for NLRP3, the key player in innate immunity. We utilized a thiophene analogue of the NLRP3 inhibitor MCC950 and employed CuAAC chemistry for the assembly of PROTACs bearing various linkers and recruiting three …

The inflammasome sensor NLRP3 interacts with REV7 to maintain genome integrity through homologous recombination Open

Delphine Burlet, Md Muntaz Khan, Sabine Hacot, Hannes Buthmann, Léa Bardoulet , et al. · 2024

DNA double strand break (DSB) is a highly toxic lesion that can generate genome instability, a major source of tumorigenesis. DSBs are mainly repaired by non-homologous end joining (NHEJ) or homologous recombination (HR). The selection of …

Development of the First-in-Class Degrader of NLRP3 Open

Tim Keuler, Dominic Ferber, Jonas Engelhardt, Christian Steinebach, Michael Marleaux , et al. · 2024

Targeted protein degradation, spearheaded by proteolysis targeting chimeras (PROTACs), has emerged as an auspicious avenue for drug discovery. NLRP3, a key player in innate immunity associated with several inflammatory diseases, has not ye…

Discovery and design of molecular glue enhancers of CDK12–DDB1 interactions for targeted degradation of cyclin K Open

Pompom Ghosh, Maximilian Schmitz, Thiyagamurthy Pandurangan, Solomon Tadesse, Sean Chin Chan , et al. · 2024

De novo design of molecular glues transforming CDK12 inhibitors, including dinaciclib, into cyclin K degraders.

Antagonistic nanobodies implicate mechanism of GSDMD pore formation and potential therapeutic application Open

Lisa D. J. Schiffelers, Yonas M. Tesfamariam, Lea‐Marie Jenster, Stefan Diehl, Sophie C. Binder , et al. · 2024

Inflammasome activation results in the cleavage of gasdermin D (GSDMD) by pro-inflammatory caspases. The N-terminal domains (GSDMD NT ) oligomerize and assemble pores penetrating the target membrane. As methods to study pore formation in l…

Structural basis of Cdk7 activation by dual T-loop phosphorylation Open

Robert Düster, K. Anand, Sophie C. Binder, Maximilian Schmitz, Karl Gatterdam , et al. · 2024

Cyclin-dependent kinase 7 (Cdk7) is required in cell-cycle and transcriptional regulation owing to its function as both a CDK-activating kinase (CAK) and part of transcription factor TFIIH. Cdk7 forms active complexes by associating with C…

The SAVED domain of the type III CRISPR protease CalpL is a ring nuclease Open

Sophie C. Binder, Niels Schneberger, Maximilian Schmitz, Marianne Engeser, Matthias Geyer , et al. · 2024

Prokaryotic CRISPR-Cas immune systems detect and cleave foreign nucleic acids. In type III CRISPR-Cas systems, the Cas10 subunit of the activated recognition complex synthesizes cyclic oligoadenylates (cOAs), second messengers that activat…

The SAVED domain of the type III CRISPR protease CalpL is a ring nuclease Open

Sophie C. Binder, Niels Schneberger, Marianne Engeser, Matthias Geyer, Christophe Rouillon , et al. · 2024

Prokaryotic CRISPR-Cas immune systems detect and cleave foreign nucleic acids. In type III CRISPR-Cas systems, the Cas10 subunit of the activated recognition complex synthesizes cyclic oligoadenylates (cOAs), second messengers that activat…

Functional diversity of <i>NLRP3</i> gain-of-function mutants associated with CAPS autoinflammation Open

Camille Cosson, Romane Riou, Danish Patoli, Tingting Niu, Amaury Rey , et al. · 2024

NLRP3-associated autoinflammatory disease is a heterogenous group of monogenic conditions caused by NLRP3 gain-of-function mutations. The poor functional characterization of most NLRP3 variants hinders diagnosis despite efficient anti-IL-1…

Supplementary Figure3 from Adipocyte Precursor-Derived NRG1 Promotes Resistance to FGFR Inhibition in Urothelial Carcinoma Open