A5086355696- Bacteriophages and microbial interactions
- Glycosylation and Glycoproteins Research
- Monoclonal and Polyclonal Antibodies Research
- Advanced biosensing and bioanalysis techniques
- SARS-CoV-2 and COVID-19 Research
- RNA and protein synthesis mechanisms
- Cellular transport and secretion
- vaccines and immunoinformatics approaches
- Cancer-related molecular mechanisms research
- MicroRNA in disease regulation
- DNA and Biological Computing
- Advanced Proteomics Techniques and Applications
- Biochemical and Structural Characterization
- Advanced Materials and Mechanics
- Protein Structure and Dynamics
- Micro and Nano Robotics
- RNA modifications and cancer
- Supramolecular Self-Assembly in Materials
- Advanced Biosensing Techniques and Applications
- Immunotherapy and Immune Responses
- Inflammasome and immune disorders
- Bacterial Genetics and Biotechnology
- RNA Interference and Gene Delivery
- Gene Regulatory Network Analysis
- Peptidase Inhibition and Analysis
National Institute of Chemistry
2016-2025
University of Ljubljana
2014-2021
Abstract Coiled-coil protein origami (CCPO) is a modular strategy for the de novo design of polypeptide nanostructures. CCPO folds are defined by sequential order concatenated orthogonal coiled-coil (CC) dimer-forming peptides, where single-chain programmed to fold into polyhedral cage. Self-assembly CC-based nanostructures from several chains, similarly as in DNA nanotechnology, could facilitate more complex assemblies and introduction functionalities. Here, we show triangular bipyramid...
Coiled-coil (CC) dimers are versatile, customizable building modules for the design of diverse protein architectures unknown in nature. Incorporation dynamic self-assembly, regulated by a selected chemical signal, represents an important challenge construction functional polypeptide nanostructures. Here, we engineered metal binding sites to render orthogonal set CC heterodimers Zn(II)-responsive as generally applicable principle. The designed peptides assemble into only presence Zn(II) ions,...
MicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally regulate the expression of target mRNAs. MicroRNA genes themselves regulated through epigenetic mechanisms, such as histone modifications and/or DNA methylation CpG islands. Aberrant island patterns frequently associated with cancer and thus researching miRNA is a topic increased research interest. Large quantities available data from various studies fragmented incomplete; therefore, integration was performed. Data 150...
The response of the adaptive immune system is augmented by multimeric presentation a specific antigen, resembling viral particles. Several vaccines have been designed based on natural or protein scaffolds, which exhibited potent to antigens; however, antibodies are also generated against scaffold, may impair subsequent vaccination. In order compare polypeptide scaffolds different size and oligomerization state with respect their efficiency, including anti-scaffold immunity, we compared...
Abstract The integration of DNA and protein‐designed nanostructures represents a transformative approach to the development programmable biopolymers for nanoscale construction. While excel in readily precision scalability base pairing, protein assemblies exploit chemical diversity amino acids greater functional versatility. Here platform is presented that unifies these two paradigms by combining coiled‐coil origami with through orthogonal protein‐protein (SpyCatcher‐SpyTag) protein‐DNA...
NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome is a multiprotein complex which forms within cells in response to various microbial self-derived triggers. Mutations the gene encoding NLRP3 cause rare cryopyrin-associated periodic syndromes (CAPS) growing evidence links common diseases such as Alzheimer´s disease. In order modulate different stages of assembly nine peptides whose sequences correspond segments components apoptosis-associated speck-like containing CARD...
Abstract Natural proteins are characterised by a complex folding pathway defined uniquely for each fold. Designed coiled-coil protein origami (CCPO) cages distinct from natural compact proteins, since their fold is prescribed discrete long-range interactions between orthogonal pairwise-interacting (CC) modules within single polypeptide chain. Here, we demonstrate that CCPO in stepwise sequential pathway. Molecular dynamics simulations and stopped-flow Förster resonance energy transfer (FRET)...
Significance Coiled-coil dimers are structural motifs which occur frequently in natural proteins. They consist of two α-helices wind around each other to form a supercoil and can be used as versatile modules for the construction designed Here, nanobodies generated against coiled-coil protein origami tetrahedral cage exhibit binding one four per dimer tetrahedron also types structures. High-resolution structures bound revealed range motifs, including positive allosteric isolated dimeric...
Several antibody-targeting cancer immunotherapies have been developed based on T cell activation at the target cells. One of most potent activators cells are bacterial superantigens, which bind to major histocompatibility complex class II antigen-presenting and activate through receptor. Strong is also one main weaknesses this strategy as it may lead systemic activation. To overcome limitation conventional antibody-superantigen fusion proteins, we split a superantigen into two fragments,...
There is an increasing research interest regarding deregulation of microRNA (miRNA) expression by DNA methylation in cancer. The aim this study was to integrate data from publications and identify miRNA genes shown be silenced the highest number cancer types thus facilitate biomarker therapeutic development. We integrated relevant 104 published scientific articles. following databases bioinformatics tools were used for analysis: miRBase, Genomic Viewer, MultAlin, SNiPer, TargetScan, Ensembl,...
To date, surface plasmon resonance (SPR) biosensors have been exploited in numerous different contexts while continuously pushing boundaries terms of improved sensitivity, specificity, portability and reusability. The latter has attracted attention as a viable alternative to disposable biosensors, also offering prospects for rapid screening biomolecules or biomolecular interactions. In this context here, we developed an approach successfully regenerate fiber-optic (FO)-SPR when utilizing...
Abstract DNA transcription is regulated by a range of diverse mechanisms and primarily factors that recruit the RNA polymerase complex to promoter region on DNA. Protein binding at nearby or distant sites can synergistically affect this process in variety ways, but mainly through direct interactions between DNA-binding proteins. Here we show Transcription Activator-Like Effector (TALE), which lacks an activation domain, enhance mammalian cells when it binds vicinity without interaction with...
Abstract Effective and safe vaccines against SARS-CoV-2 are highly desirable to prevent casualties societal cost caused by Covid-19 pandemic. The receptor binding domain (RBD) of the surface-exposed spike protein represents a suitable target for induction neutralizing antibodies upon vaccination. Small antigens typically induce weak immune response while particles measuring tens nanometers efficiently presented B cell follicles subsequently follicular germinal center cells in draining lymph...
Spike trimer plays a key role in SARS-CoV-2 infection and vaccine development. It consists of globular head flexible stalk domain that anchors the protein into viral membrane. While has been extensively studied, properties adjoining are poorly understood. Here, we characterize coiled-coil formation thermodynamic stability its segments. We find N-terminal segment does not form coiled-coils remains disordered solution. The C-terminal forms trimeric solution, which becomes significantly...
Abstract Versatile DNA and polypeptide‐based structures have been designed based on complementary modules. However, polypeptides can also form higher oligomeric states. We investigated the introduction of tetrameric modules as a substitute for coiled‐coil dimerization units used in previous modular nanostructures. Tetramerizing helical bundles run parallel or antiparallel orientation, expanding number topological solutions Furthermore, this strategy facilitates construction nanostructures...
Abstract Versatile DNA and polypeptide‐based structures have been designed based on complementary modules. However, polypeptides can also form higher oligomeric states. We investigated the introduction of tetrameric modules as a substitute for coiled‐coil dimerization units used in previous modular nanostructures. Tetramerizing helical bundles run parallel or antiparallel orientation, expanding number topological solutions Furthermore, this strategy facilitates construction nanostructures...
Dataset includes: Topologies-circular-permutations-TCO.xlsx – List of topologies and circular permutations in file CC-protein-origami.fasta all the design sequences fasta format. all-atom-models.zip representative models generated by CoCoPOD, including with best fit to SAXS data SAXS-data.zip scattering curves constructs presented main article. electron-reconstruction negative stain density reconstructions. electron-reconstruction.zip - contains reconstituted electron microscopy densities...
A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-21969-9