Volker Dötsch

eLife Assessment: Distinct allosteric remodeling of HIV-1 Env dynamics on virions by gp41-directed antibodies reveals two modes of neutralization

Volker Dötsch

HIV-1 envelope glycoprotein (Env), a gp120–gp41 trimer, undergoes coordinated conformational changes that drive membrane fusion and allow immune evasion by transiently concealing neutralization-sensitive epitopes. Most broadly neutralizing antibodies (bNAbs) target gp120, whereas a distinct subset recognizes conserved gp41 regions, such as the …

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eLife Assessment: Cell cycle-coupled CK1δ turnover, autoinhibition, and activity

Volker Dötsch

Casein kinase 1δ (CK1δ) is a ubiquitously expressed kinase involved in diverse cellular processes, including cell cycle regulation. CK1δ activity is attenuated by (auto)phosphorylation. However, inhibitory phosphorylation is efficiently opposed by cellular phosphatases as CK1δ accumulates in its hypophosphorylated, active state. CK1δ …

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eLife Assessment: Opto-MDMi: a dual-lock optogenetic system for robust activation of endogenous p53

Volker Dötsch

Optogenetics has emerged as a powerful technology for manipulating biological functions with high spatiotemporal resolution, yet the precise control of endogenous molecules remains a significant challenge. In this study, we developed Opto-MDMi, a dual-lock optogenetic platform designed to control the activity of …

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eLife Assessment: Structural basis for site-specific histone H3 acetylation-dependent regulation of RNAPII transcription through nucleosomes

Volker Dötsch

Acetylation of histone H3 regulates chromatin dynamics and transcription, but how specific acetylation sites affect RNA polymerase II (RNAPII) transcription through nucleosomes remains unclear. Here, we found that H3 acetylation at Lys56 and Lys122 markedly enhances RNAPII transcription through nucleosomes, whereas acetylation …

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DARPins as pan-reactivators of temperature-sensitive p53 cancer mutants

Philipp Münick, Dimitrios-Ilias Balourdas, Julianne S Funk, Büşra Yüksel et autres

The tumor suppressor p53 is the most frequently mutated protein in tumors and a target for drug development. More than 2000 cancer-associated p53 missense mutations have been reported, most of them located in the DNA-binding domain (DBD). Due to the low intrinsic …

DARPins as pan-reactivators of temperature-sensitive p53 cancer mutants

Philipp Münick, Dimitrios-Ilias Balourdas, Julianne S Funk, Büşra Yüksel et autres

The tumor suppressor p53 is the most frequently mutated protein in tumors and a target for drug development. More than 2000 cancer-associated p53 missense mutations have been reported, most of them located in the DNA-binding domain (DBD). Due to the low intrinsic …

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eLife Assessment: Distinct allosteric remodeling of HIV-1 Env dynamics on virions by gp41-directed antibodies reveals two modes of neutralization

Volker Dötsch

HIV-1 envelope glycoprotein (Env), a gp120–gp41 trimer, undergoes coordinated conformational changes that drive membrane fusion and allow immune evasion by transiently concealing neutralization-sensitive epitopes. Most broadly neutralizing antibodies (bNAbs) target gp120, whereas a distinct subset recognizes conserved gp41 regions, such as the …

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Overcoming Ligand Discovery Challenges: Developing Peptide-Based Tracers for SPSB2

Christopher Lenz, Lewis Elson, Johannes Dopfer, Frederic Farges et autres

High Resolution Image Download MS PowerPoint Slide Developing new E3 ligase ligands for the design of heterobivalent molecules, such as PROteolysis TArgeting Chimeras (PROTACs), requires careful evaluation of target engagement (TE). Characterizing protein–protein interactions (PPIs) is therefore essential in drug discovery, as …

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eLife Assessment: Twelve phosphomimetic mutations induce the assembly of recombinant full-length human tau into paired helical filaments

Volker Dötsch

The assembly of tau into amyloid filaments is associated with more than twenty neurodegenerative diseases, collectively termed tauopathies. Cryo-EM structures of brain-derived tau filaments revealed that specific structures define different diseases, triggering a quest for the development of experimental model systems that …

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Bacterial polyphosphates impede the macrophage response to infection 2084

Markus Bosmann, Julian Röwe, Kevin Brueck, Archana Jayaraman et autres

Abstract Description Sepsis affects ∼50 million people annually, with mortality rates of 20–50%. Host-pathogen interactions are implicated in its etiology but are understudied. Bacterial polyphosphates are metabolites with pleiotropic functions in stress response, virulence and host evasion. Here, we reveal polyphosphate-mediated changes …

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eLife Assessment: Active regulation of the epidermal growth factor receptor by the membrane bilayer

Volker Dötsch

Cell surface receptors transmit information across the plasma membrane to connect the extracellular environment to intracellular function. While the structures and interactions of the receptors have been long established as mediators of signaling, increasing evidence suggests that the membrane itself plays an …

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eLife Assessment: Structural evolution of nitrogenase over 3 billion years

Volker Dötsch

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