Research Area D - Publications 2017

Immunity, Volume 47, Issue 6, p1067–1082.e12,
Immunity, online article


Roquin proteins preclude spontaneous T cell activation and aberrant differentiation of T follicular helper (Tfh) or T helper 17 (Th17) cells. Here we showed that deletion of Roquin-encoding alleles specifically in regulatory T (Treg) cells also caused the activation of conventional T cells. Roquin-deficient Treg cells downregulated CD25, acquired a follicular ...


Journal of Molecular Biology, Volume 429, Issue 24, Pages 3814-3824,
Journal of Molecular Biology, online article


Ubiquitination is a multifunctional posttranslational modification controlling the activity, subcellular localization and stability of proteins. The E3 ubiquitin ligase ubiquitin-like PHD and RING finger domain-containing protein 1 (UHRF1) is an essential epigenetic factor that recognizes repressive histone marks as well as hemi-methylated DNA and recruits DNA ...


J. Bacteriol., vol. 200, no. 2 e00599-17, doi: 10.1128/JB.00599-17
J. Bacteriol., online article


The peptide transporter carbon starvation (CstA) family (transporter classification [TC] 2.A.114) belongs to the second largest superfamily of secondary transporters, the amino acid/polyamine/organocation (APC) superfamily. No representative of the CstA family has previously been characterized either biochemically or structurally, but we have now identified the ...


J. Bacteriol., vol. 200 no. 1 e00536-17, doi: 10.1128/JB.00536-17
J. Bacteriol., online article


Fluctuating environments and individual physiological diversity force bacteria to constantly adapt and optimize the uptake of substrates. We focus here on two very similar two-component systems (TCSs) of Escherichia coli belonging to the LytS/LytTR family: BtsS/BtsR (formerly YehU/YehT) and YpdA/YpdB. Both TCSs respond to extracellular pyruvate, albeit with ...


eLife 2017;6:e29736, doi: 10.7554/eLife.29736
eLife, online article


Gene transcription can be activated by decreasing the duration of RNA polymerase II pausing in the promoter-proximal region, but how this is achieved remains unclear. Here we use a 'multi-omics' approach to demonstrate that the duration of polymerase pausing generally limits the productive frequency of transcription initiation in human cells ('pause-initiation ...


mBio, vol. 8, no. 5 e01412-17, doi: 10.1128/mBio.01412-17
mBio, online article


Glycosylation is a universal strategy to posttranslationally modify proteins. The recently discovered arginine rhamnosylation activates the polyproline-specific bacterial translation elongation factor EF-P. EF-P is rhamnosylated on arginine 32 by the glycosyltransferase EarP. However, the enzymatic mechanism remains elusive. In the present study, we solved the ...


PNAS, vol. 114, no. 40,
PNAS, online article


Successful pathogens use complex signaling mechanisms to monitor their environment and reprogram global gene expression during specific stages of infection. Group A Streptococcus (GAS) is a major human pathogen that causes significant disease burden worldwide. A secreted cysteine protease known as streptococcal pyrogenic exotoxin B (SpeB) is a key virulence ...


Nature, 549, 394–398, doi:10.1038/nature23890
Nature, online article


Cytosolic DNA arising from intracellular pathogens triggers a powerful innate immune response. It is sensed by cyclic GMP–AMP synthase (cGAS), which elicits the production of type I interferons by generating the second messenger 2′3′-cyclic-GMP–AMP (cGAMP). Endogenous nuclear or mitochondrial DNA can also be sensed by cGAS under certain conditions, resulting in ...


Molecular Cell, Volume 67, Issue 4, p550–565.e5,
Molecular Cell, online article


DNA methylation is an essential epigenetic mark in mammals that has to be re-established after each round of DNA replication. The protein UHRF1 is essential for this process; it has been proposed that the protein targets newly replicated DNA by cooperatively binding hemi-methylated DNA and H3K9me2/3, but this model leaves a number of questions unanswered. Here, ...


PLoS ONE, 12(8): e0182993,
PLoS ONE, online article


Bacterial histidine kinase/response regulator systems operate at the interface between environmental cues and physiological states. Escherichia coli contains two LytS/LytTR-type histidine kinase/response regulator systems, BtsS/BtsR (formerly YehU/YehT) and YpdA/YpdB, which have been identified as pyruvate-responsive two-component systems. Since they exhibit ...


Molecular Microbiology, Volume 106, Issue 1, Pages 54–73, DOI: 10.1111/mmi.13751
Molecular Microbiology, online article


The two-component system KdpD/KdpE governs K+ homeostasis by controlling synthesis of the high affinity K+ transporter KdpFABC. When sensing low environmental K+ concentrations, the dimeric kinase KdpD autophosphorylates in trans and transfers the phosphoryl-group to the response regulator KdpE, which subsequently activates kdpFABC transcription. In Escherichia ...


Nature Chemistry, doi:10.1038/nchem.2811
Nature Chemistry, online article


Functional antibody delivery in living cells would enable the labelling and manipulation of intracellular antigens, which constitutes a long-thought goal in cell biology and medicine. Here we present a modular strategy to create functional cell-permeable nanobodies capable of targeted labelling and manipulation of intracellular antigens in living cells. The ...


The EMBO Journal, DOI 10.15252/embj.201695757
The EMBO Journal, online article


Replacement of canonical histones with specialized histone variants promotes altering of chromatin structure and function. The essential histone variant H2A.Z affects various DNA-based processes via poorly understood mechanisms. Here, we determine the comprehensive interactome of H2A.Z and identify PWWP2A as a novel H2A.Z-nucleosome binder. PWWP2A is a ...


Nature Communications, 8, Article number: 15760, doi:10.1038/ncomms15760
Nature Communications, online article


Histone H2AX phosphorylation is an early signalling event triggered by DNA double-strand breaks (DSBs). To elucidate the elementary units of phospho-H2AX-labelled chromatin, we integrate super-resolution microscopy of phospho-H2AX during DNA repair in human cells with genome-wide sequencing analyses. Here we identify phospho-H2AX chromatin domains in the ...


American Association for Cancer Research, Print ISSN 0008-5472, DOI: 10.1158/0008-5472.CAN-16-1922
American Association for Cancer Research, online article


Inherent intermediate-to-low affinity T cell receptors (TCR) that develop during the natural course of immune responses may not allow sufficient activation for tumor elimination, making the majority of T cells suboptimal for adoptive T cell therapy (ATT). TCR affinity enhancement has been implemented to provide stronger T cell activity but carries the risk of ...


Scientific Reports, 7, Article number: 1684, doi:10.1038/s41598-017-01943-6
Scientific Reports, online article


The bromodomain protein Brd4 is an epigenetic reader and plays a critical role in the development and maintenance of leukemia. Brd4 binds to acetylated histone tails and activates transcription by recruiting the positive elongation factor P-TEFb. Small molecule inhibitor JQ1 competitively binds the bromodomains of Brd4 and displaces the protein from acetylated ...


Scientific Reports, 7, Article number: 1388, doi:10.1038/s41598-017-01410-2
Scientific Reports, online article


Two-component systems are crucial for signal perception and modulation of bacterial behavior. Nevertheless, to date, very few ligands have been identified that directly interact with histidine kinases. The histidine kinase/response regulator system YehU/YehT of Escherichia coli is part of a nutrient-sensing network. Here we demonstrate that this system senses the ...


PNAS, vol. 114 no. 20,  E3944-E3953, doi: 10.1073/pnas.1700128114
PNAS, online article


The carboxyl-terminal domain (CTD) of the largest subunit of RNA polymerase II (Pol II) orchestrates dynamic recruitment of specific cellular machines during different stages of transcription. Signature phosphorylation patterns of Y1S2P3T4S5P6S7 heptapeptide repeats of the CTD engage specific “readers.” Whereas phospho-Ser5 and phospho-Ser2 marks are ubiquitous, ...


Scientific Reports, 7, Article number: 1051, doi:10.1038/s41598-017-01031-9
Scientific Reports, online article


The transmembrane DNA-binding protein CadC of E. coli, a representative of the ToxR-like receptor family, combines input and effector domains for signal sensing and transcriptional activation, respectively, in a single protein, thus representing one of the simplest signalling systems. At acidic pH in a lysine-rich environment, CadC activates the transcription of ...


Front. Microbiol., Volume 8, Article 634, doi: 10.3389/fmicb.2017.00634
Front. Microbiol., online article


Quorum sensing (QS) is a process enabling a bacterial population to communicate via small molecules called autoinducers (AIs). This intercellular communication process allows single cells to synchronize their behavior within a population. The marine bacterium Vibrio harveyi ATCC BAA-1116 channels the information of three AI signals into one QS cascade. Three ...


Nature Protocols, 12, 1011–1028, doi:10.1038/nprot.2017.020
Nature Protocols, online article


3D structured illumination microscopy (3D-SIM) is the super-resolution technique of choice for multicolor volumetric imaging. Here we provide a validated sample preparation protocol for labeling nuclei of cultured mammalian cells, image acquisition and registration practices, and downstream image analysis of nuclear structures and epigenetic marks. Using ...


Nature Structural & Molecular Biology, 24, 341–343, doi:10.1038/nsmb.3394
Nature Structural & Molecular Biology, online article


Chromatin-remodeling enzymes perform the formidable task of reorganizing the structure of a stable macromolecular assembly, the nucleosome. Recently published work demonstrates that the SNF2H chromatin remodeler distorts the histone octamer structure upon binding to the nucleosome, then taps into this induced plasticity to productively achieve nucleosome sliding.


Molecular Plant, Volume 10, Issue 4, p575–589,
Molecular Plant, online article


The translocon on the outer membrane of mitochondria (TOM) facilitates the import of nuclear-encoded proteins. The principal machinery of mitochondrial protein transport seems conserved in eukaryotes; however, divergence in the composition and structure of TOM components has been observed between mammals, yeast, and plants. TOM9, the plant homolog of yeast Tom22, ...


Chem. Sci., 8, 3471, DOI: 10.1039/c7sc00574a
Chem. Sci., online article


The broad substrate tolerance of tubulin tyrosine ligase is the basic rationale behind its wide applicability for chemoenzymatic protein functionalization. In this context, we report that the wild-type enzyme enables ligation of various unnatural amino acids that are substantially bigger than and structurally unrelated to the natural substrate, tyrosine, without ...


Hum Mol Genet., 26 (8): 1522-1534; DOI:
Hum Mol Genet., online article


DNMT1 is recruited to substrate sites by PCNA and UHRF1 to maintain DNA methylation after replication. The cell cycle dependent recruitment of DNMT1 is mediated by the PCNA-binding domain (PBD) and the targeting sequence (TS) within the N-terminal regulatory domain. The TS domain was found to be mutated in patients suffering from hereditary sensory and autonomic ...


ACS Synth. Biol., 6 (5), pp 826–836, DOI: 10.1021/acssynbio.6b00323
ACS Synth. Biol., online article


Natural and synthetic scaffolds support enzyme organization in complexes, and they regulate their function and activity. Here we report that CipA and CipB, two small proteins that form protein crystalline inclusions (PCIs) in the cytoplasm of Photorhabdus luminescens, can be utilized as scaffolds to efficiently incorporate exogenous proteins into PCIs. We ...


Molecular Cell, Volume 65, Issue 4, p631–643.e4,
Molecular Cell, online article


Single-cell RNA sequencing (scRNA-seq) offers new possibilities to address biological and medical questions. However, systematic comparisons of the performance of diverse scRNA-seq protocols are lacking. We generated data from 583 mouse embryonic stem cells to evaluate six prominent scRNA-seq methods: CEL-seq2, Drop-seq, MARS-seq, SCRB-seq, Smart-seq, and ...


Nature Chemical Biology, doi:10.1038/nchembio.2282
Nature Chemical Biology, online article


Protein lysine methyltransferases (PKMTs) regulate diverse physiological processes including transcription and the maintenance of genomic integrity. Genetic studies suggest that the PKMTs SUV420H1 and SUV420H2 facilitate proficient nonhomologous end-joining (NHEJ)-directed DNA repair by catalyzing the di- and trimethylation (me2 and me3, respectively) of lysine ...


Molecular Microbiology, 104(1), 16–31 , doi:10.1111/mmi.13597
Molecular Microbiology, online article


BceRS and PsdRS are paralogous two-component systems in Bacillus subtilis controlling the response to antimicrobial peptides. In the presence of extracellular bacitracin and nisin, respectively, the two response regulators (RRs) bind their target promoters, PbceA or PpsdA, resulting in a strong up-regulation of target gene expression and ultimately antibiotic ...


MicrobiologyOpen, Volume 6, Issue 3, e00438, DOI: 10.1002/mbo3.438
MicrobiologyOpen, online article


Two-component signal transduction constitutes the predominant strategy used by bacteria to adapt to fluctuating environments. The KdpD/KdpE system is one of the most widespread, and is crucial for K+ homeostasis. In Escherichia coli, the histidine kinase KdpD senses K+ availability, whereas the response regulator KdpE activates synthesis of the high-affinity K+ ...


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Helmholtz München
MPI of Neurobiology
MPI of Biochemistry