A5049334425- DNA Repair Mechanisms
- DNA and Nucleic Acid Chemistry
- interferon and immune responses
- Bacterial Genetics and Biotechnology
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Immune Response and Inflammation
- Enzyme Structure and Function
- Inorganic Chemistry and Materials
- CRISPR and Genetic Engineering
- PARP inhibition in cancer therapy
- Cancer therapeutics and mechanisms
- Antimicrobial Resistance in Staphylococcus
- Inflammasome and immune disorders
- Cancer-related Molecular Pathways
- NF-κB Signaling Pathways
- Nanoplatforms for cancer theranostics
- Glycosylation and Glycoproteins Research
- T-cell and B-cell Immunology
- RNA Interference and Gene Delivery
- Signaling Pathways in Disease
- Cell death mechanisms and regulation
- Ubiquitin and proteasome pathways
- Cytokine Signaling Pathways and Interactions
- Phenothiazines and Benzothiazines Synthesis and Activities
Ludwig-Maximilians-Universität München
2016-2025
Center for Integrated Protein Science Munich
2007-2022
Gene Therapy Laboratory
2009-2022
Immunoglobulins recognize and clear microbial pathogens toxins through the coupling of variable region specificity to Fc-triggered cellular activation. These proinflammatory activities are regulated, thus avoiding pathogenic sequelae uncontrolled inflammation by modulating composition Fc-linked glycan. Upon sialylation, affinities for Fcγ receptors reduced, whereas those alternative receptors, such as dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin...
Neuromyelitis optica is a paradigmatic autoimmune disease of the central nervous system, in which water-channel protein AQP4 target antigen
Toll-like receptor 7 (TLR7) is essential for recognition of RNA viruses and initiation antiviral immunity. TLR7 contains two ligand-binding pockets that recognize different degradation products: pocket 1 recognizes guanosine, while 2 coordinates pyrimidine-rich fragments. We found the endonuclease RNase T2, along with 5′ exonucleases PLD3 PLD4, collaboratively generate ligands TLR7. Specifically, T2 generated guanosine 2′,3′-cyclic monophosphate-terminated PLD exonuclease activity further...
DNA polymerase η (Pol η) is a eukaryotic lesion bypass that helps organisms to survive exposure ultraviolet (UV) radiation, and tumor cells gain resistance against cisplatin-based chemotherapy. It allows replicate across cross-link lesions such as 1,2-d(GpG) cisplatin adducts (Pt-GG) UV-induced cis – syn thymine dimers. We present structural biochemical analysis of how Pol copies Pt-GG–containing DNA. The damaged bound in an open binding rim. Nucleotidyl transfer requires the rotate into...
RIG-I and MDA5 sense cytoplasmic viral RNA set-off a signal transduction cascade, leading to antiviral innate immune response. The third RIG-I-like receptor, LGP2, differentially regulates RIG-I- MDA5-dependent sensing in an unknown manner. All three receptors possess C-terminal regulatory domain (RD), which the case of senses pattern 5′-triphosphate activates ATP-dependent signaling by RIG-I. Here we report 2.6 Å crystal structure LGP2 RD along with vitro vivo functional analyses homology...
Abstract Schlafen 11 (SLFN11) is an interferon-inducible antiviral restriction factor with tRNA endoribonuclease and DNA binding functions. It recruited to stalled replication forks in response stress inhibits of certain viruses such as the human immunodeficiency virus 1 (HIV-1) by modulating pool. SLFN11 has been identified a predictive biomarker cancer, its expression correlates beneficial damage inducing anticancer drugs. However, mechanism interdependence these two functions are largely...
DNA double-strand breaks (DSBs) threaten genome stability in all kingdoms of life and are linked to cancerogenic chromosome aberrations humans. The Mre11:Rad50 (MR) complex is an evolutionarily conserved two Rad50 ATPases a dimer the Mre11 nuclease that senses processes DSBs tethers for repair. ATP binding hydrolysis by functionally coupled DNA-binding tethering, but also regulates Mre11's processing ends. To understand how controls interaction between Rad50, we determined crystal structure...
Second site: In the crystal structure of human MALT1casp-Ig3 (mucosa-associated lymphoid tissue lymphoma translocation protein 1) in complex with tricyclic phenothiazine derivative thioridazine (violet picture), inhibitor is bound a hydrophobic pocket far from active site. This explains action derivatives as noncompetitive, reversible inhibitors. As service to our authors and readers, this journal provides supporting information supplied by authors. Such materials are peer reviewed may be...
The CARD11-BCL10-MALT1 (CBM) complex triggers the adaptive immune response in lymphocytes and lymphoma cells. CARD11/CARMA1 acts as a molecular seed inducing BCL10 filaments, but integration of MALT1 assembly functional CBM has remained elusive. Using cryo-EM we solved helical structure BCL10-MALT1 filament. structural model filament core at 4.9 Å resolution identified interface between N-terminal DD caspase recruitment domain. C-terminal Ig paracaspase domains protrude from this to...
Oligoadenylate synthetase (OAS) proteins are immune sensors for double-stranded RNA and critical restricting viruses. OAS2 comprises two OAS domains, only one of which can synthesize 2'-5'-oligoadenylates RNase L activation. Existing structures OAS1 provide a model enzyme activation, but do not explain how multiple domains discriminate length. Here, we discover that exists in an autoinhibited state as zinc-mediated dimer present mechanism length discrimination: the catalytically deficient...
Summary The MRE11-RAD50-NBS1 (MRN) complex is a central, multifunctional factor in the detection, signaling and nucleolytic processing of DNA double-strand breaks (DSBs). To clarify how human MRN binds generic telomeric ends can separate end sensing from nuclease activities, we determined cryo-electron microscopy structures bound to telomere protection TRF2. senses DSBs through tight clamp-like state with closed coiled-coil domains, but auto-inhibited MRE11 nuclease. NBS1 wraps around dimer,...
The Schlafen family belongs to the interferon-stimulated genes and its members are involved in cell cycle regulation, T quiescence, inhibition of viral replication, DNA-repair tRNA processing. Here, we present cryo-EM structure full-length human 5 (SLFN5) high-resolution crystal highly conserved N-terminal core domain. We show that domain does not resemble an ATPase-like fold neither binds nor hydrolyzes ATP. SLFN5 as well single- double-stranded DNA, suggesting a potential role...
The innate immune sensor retinoic acid-inducible gene I (RIG-I) detects cytosolic viral RNA and requires a conformational change caused by both ATP binding to induce an active signaling state trigger response. Previously, we showed that hydrolysis removes RIG-I from lower-affinity self-RNAs (<xref ref-type="bibr" rid="bib19">Lässig et al., 2015</xref>), revealing how turnover helps distinguish self-RNA explaining why mutation in motif slows down causes the autoimmune disease Singleton-Merten...