Department of Biology, Chemistry, Pharmacy

Horatscheck et al. developed and characterized next-generation clathrin inhibitors, Pitstop 2c and 2d, which block endocytic protein binding, inhibiting receptor-mediated endocytosis and vesicular stomatitis virus entry with minimal toxicity. These compounds offer improved tools for studying clathrin function and potential antiviral applications.

Since 2003, the Macromolecular Crystallography (MX) group at Helmholtz-Zentrum Berlin has operated three MX beamlines at BESSY II. Continuously developed over two decades, these beamlines enable advanced diffraction experiments. Used by over 100 research groups, they have contributed to more than 4,500 Protein Data Bank depositions. Mueller et al. explore the history, current status and future directions of the facilities.

Drozdz et al. show that phosphorylation cascades can target the splicing machinery and lead to the fast and transient adjustment in the alternative splicing program of cells. The process is coined “immediate early splicing” and can help, e.g., to coordinate the extensive changes in gene expression during T cell activation. The findings set a paradigm for a new gene regulatory principle in the cellular response to activation.

Wang et al. find that ADP and (p)ppGpp nucleotides bound at subunit interfaces inhibit ρ ring closure that underpins the hexamer activation, thus favoring the assembly of inactive higher-order oligomers. Connector substitutions and antibiotics that inhibit RNA and protein syntheses trigger ρ aggregation in the cell. These and other recent data implicate aggregation as a widespread strategy to tune ρ activity.

Many bacteriophages can modulate host transcription. Gjorgjevikj et al. uncover the anti-termination mechanism of phage satellite P4 protein, Psu. Psu dimers clamp two open rings of the termination factor ρ, promote ρ hyper-oligomerization, and trap nucleotides in ρ’s binding pockets.

The active zone is a brain signaling hub critical for synaptic information transfer and the encoding of behaviors. Lützkendorf et al. identify Blobby as an assembly factor required for proper active zone nanoscale protein architecture and memory formation.

Crystallographic fragment screening (CFS) has recently matured into an important method for the early stages of drug discovery projects. Barthel et al. describe the specialized F2X workflow along with the relevant differences to other existing CFS platforms, and the ongoing developments aimed at supporting users of the facility.

Stockhammer, Adarska et al describe ARF1 compartments as the site of adaptor- and clathrin-dependent post-Golgi sorting. Shedding of ARF1 and maturation into recycling endosomes drives sorting of secretory and endocytic recycling cargo.

Here we provide a resource for endogenous tagging with TurboID for proximity-based proteomics

STED imaging of endogenously tagged ARF GTPases reveals their distinct nanoscale localizations

How Can the Diterpene Synthase CotB2V80L Alter the Product Profile?

We here developed an open source, high-resolution, automated fluorescence microscope that fits into an incubator and can be built mostly from low-cost components.

Using single particle tracking and simulations, we tested here a long-standing assumption, that the submembrane cytoskeleton compartmentalizes the motion of membrane proteins. We could find that in several neuronal cell types submembrane actin rings impede the lateral motion of membrane proteins.

We here developed a synthetic virus-receptor system to ask, if multivalent lipid binding alone is sufficient for viral internalization. By tuning receptor affinity, we could show that once a threshold in adhesion energy is met, particles deform the plasma membrane and internalize. We could thus identify a purely biophysical path to enter cells.

We here developed a method for the controlled optogenetic delivery of any protein at the single molecule level.

Dynamic remodeling of Septin structures fine-tunes myogenic differentiation

Combining genetics and RNA sequencing in this joint study with the Leah Cowen lab at the University of Toronto we link the virulence-associated filamentation program of the opportunistic fungal pathogen Candida albicans to pre-mRNA splicing.

Ilhan M., Hastar N., Kampfrath B., Spierling D. N., Jatzlau J., Knaus P..BMP Stimulation Differentially Affects Phosphorylation and Protein Stability of β-Catenin in Breast Cancer Cell Lines. Int. J. Mol. Sci. 2024, 25(9), 4593

Concerted transformation of a hyper-paused transcription complex and its reinforcing protein

In this joint review with the Karla Neugebauer lab at Yale University we discuss co-transcriptional gene regulation in both prokaryotes and eukaryotes and highlight striking parallels in how RNA polymerases interact with the machineries that act on nascent RNA.

The Stricker group shows a critical requirement for Neurofibromin to coordinate muscle fiber growth and muscle stem cell quiescence induction, and to prevent detrimental metabolic reprogramming with life-long consequences.

Fluid Shear Stress-modulated chromatin accessibility reveals the mechano-dependency of endothelial SMAD1/5-mediated gene transcription

The Stricker group provides a new model for lymph node initiation in the embryo

3D surface reconstruction of cellular cryo-soft X-ray microscopy tomograms using semisupervised deep learning

Controlled Grafting Expansion Microscopy

In this paper by Abualrous et al., catalyzed peptide exchange, a process that shapes T cell responses, is reported for 12 different MHC class II variants. Experimental approaches taken by the Freund laboratory are combined with a theoretical description by the Noe group. It is shown that the population of a transient state has predictive value for catalyzed exchange and that MHC class II dynamics correlates with the odds ratio for the autoimmune disease rheumatoid arthritis.

Modulation of RNA binding properties of the RNA helicase UPF1 by its activator UPF2

Extended DNA threading through a dual-engine motor module of the activating signal co-integrator 1 complex

Conformation-dependent ligand hot spots in the spliceosomal RNA helicase, BRR2

Jatzlau & Burdzinski et al. have established techniques for visualization of TGFβ superfamily receptors and growth factors

Branch point strength controls species-specific CAMK2B alternative splicing and regulates LTP

A human kinase yeast array for the identification of kinases modulating phosphorylation-dependent protein–protein interactions

The molecular and phenotypic spectrum of CLCN4-related epilepsy

Exchange catalysis by tapasin exploits conserved and allele-specific features of MHC-I molecules

Large-scale ratcheting in a bacterial DEAH/RHA-type RNA helicase that modulates antibiotics susceptibility

Long-range allostery mediates cooperative adenine nucleotide binding by the Ski2-like RNA helicase Brr2

Differential Impact of Fluid Shear Stress and YAP/TAZ on BMP/TGF‐β Induced Osteogenic Target Genes

ActivinA Induced SMAD1/5 Signaling in an iPSC Derived EC
Model of Fibrodysplasia Ossificans Progressiva (FOP) Can Be Rescued by the
Drug Candidate Saracatinib

Left-handed DNA-PAINT for improved super-resolution imaging in the nucleus

Directed manipulation of membrane proteins by fluorescent magnetic nanoparticles

The δ subunit and NTPase HelD institute a two-pronged mechanism for RNA polymerase recycling

A skipping rope translocation mechanism in a widespread family of DNA repair helicases
Roske in Nucleic Acids Research

Loll in JACS: The Impression of a Nonexisting Catalytic Effect: The Role of CotB2 in Guiding the Complex Biosynthesis of Cyclooctat-9-en-7-ol

Steps toward translocation-independent RNA polymerase inactivation by terminator ATPase ρ

Neumann in EMBO Reports
Neumann, Heyd, Preußner - Alternative splicing coupled mRNA decay shapes
the temperature‐dependent transcriptome

Stricker in Journal of Cachexia, Sarcopenia and Muscle: Cell autonomous requirement of neurofibromin (Nf1) for postnatal muscle hypertrophic growth and metabolic homeostasis

Hiepen, Mendes, Knaus in Cells:
"It Takes Two to Tango:
Endothelial TGFβ/BMP Signaling Crosstalk with Mechanobiology"

Huang - Structure-Based Mechanisms of a Molecular RNA Polymerase/Chaperone Machine Required for Ribosome Biosynthesis

Freund in Brain
Syntaxin-1B mutations reveal clear molecular disease mechanisms that translate into distinct neurophysiological phenotypes

Knaus in Bone
BMP signalling in a mechanical context – Implications for bone biology

Meinke et al, in eLife
Srsf10 and the minor spliceosome control
tissue-specific and dynamic SR protein expression

Tom Haltenhof et al. in Molecular Cell: A conserved kinase-based body
temperature sensor globally controls alternative splicing and gene
expression

Knaus-AMOT130 drives BMP-SMAD signaling at the apical membrane in polarized cells

Hiepen-BMPR2 acts as a gatekeeper to protect endothelial cells from increased TGFβ responses and altered cell mechanics

Chakrabarti - Insights into the assembly and architecture of a Staufen-mediated mRNA decay (SMD)-competent mRNP

Loll - Current understanding and biotechnological application of the bacterial diterpene synthase CotB2

Wahl - Structural basis for the function of SuhB as a transcription factor in ribosomal RNA synthesis

Freund - Exon Inclusion Modulates Conformational Plasticity and Autoinhibition of the Intersectin 1 SH3A Domain

Stauber - A FRET sensor of C-terminal movement reveals VRAC activation by plasma membrane DAG signaling rather than ionic strength

F. De Bortoli - Increased versatility despite reduced molecular complexity: evolution, structure and function of metazoan splicing factor PRPF39

A. Neumann - Genome-wide identification of
alternative splicing events that regulate protein transport across the
secretory pathway

J. Sticht - FBP21’s C-Terminal Domain Remains Dynamic When Wrapped around the c-Sec63 Unit of Brr2 Helicase

R. Driller - Towards a comprehensive understanding of the
structural dynamics of a bacterial diterpene
synthase during catalysis

S. Stricker - Odd skipped-related 1 (Osr1) identifies muscle-interstitial fibro-adipogenic progenitors (FAPs) activated by acute injury

B. Loll - Molecular insights into antibiotic resistance - how a binding protein traps albicidin

S. Stricker - Genome-wide strategies identify downstream target genes of connective tissue-associated transcription factors

Sigmar Stricker - Cooperation of BMP and IHH signaling in interdigital cell fate determination

Jan Wollenhaupt - Intrinsically Disordered Protein Ntr2 Modulates the Spliceosomal RNA Helicase Brr2

B. Loll: Ketonization of Proline Residues in the Peptide Chains of Actinomycins by a 4-Oxoproline Synthase

B. Loll: Rhodococcus erythropolis Oleate Hydratase: a New Member in the Oleate Hydratase Family Tree