A5018850454- Glycosylation and Glycoproteins Research
- Bacteriophages and microbial interactions
- Advanced biosensing and bioanalysis techniques
- Monoclonal and Polyclonal Antibodies Research
- Cellular transport and secretion
- Protein Structure and Dynamics
- DNA Repair Mechanisms
- RNA and protein synthesis mechanisms
- Bacterial Genetics and Biotechnology
- Virus-based gene therapy research
- DNA and Nucleic Acid Chemistry
- Advanced Materials and Mechanics
- thermodynamics and calorimetric analyses
- Biochemical and Structural Characterization
- ATP Synthase and ATPases Research
- Respiratory viral infections research
- Supramolecular Self-Assembly in Materials
- Peptidase Inhibition and Analysis
- Enzyme Structure and Function
- Micro and Nano Robotics
- Immune Response and Inflammation
- RNA Interference and Gene Delivery
- Microtubule and mitosis dynamics
- Antimicrobial Peptides and Activities
- Biochemical and Molecular Research
National Institute of Chemistry
2016-2024
University of Nova Gorica
2022-2023
EN-FIST Centre of Excellence (Slovenia)
2020-2022
University of Ljubljana
2018
University of Bologna
2015-2016
The structure–activity relationship was investigated in a series of synthetic TLR4 antagonists formed by glucosamine core linked to two phosphate esters and linear carbon chains. Molecular modeling showed that the compounds with 10, 12, 14 carbons chains are associated higher stabilization MD-2/TLR4 antagonist conformation than case C16 variant. Binding experiments human MD-2 C12 C14 variants have affinity C10, while variant did not interact protein. molecules, exception variant, inhibited...
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,...
The rational design of supramolecular assemblies aims to generate complex systems based on the simple information encoded in chemical structure. Programmable molecules such as nucleic acids and polypeptides are particularly suitable for designing diverse shapes not found nature. Here, we describe a strategy assembling modular architectures structurally covalently preorganized subunits. Cyclization through spontaneous self-splicing split intein coiled-coil dimer-based interactions polypeptide...
Abstract Coiled-coil (CC) dimer-forming peptides are attractive designable modules for mediating protein association. Highly stable CCs desired biological activity regulation and assay. Here, we report the design versatile applications of orthogonal CC with a dissociation constant in low nanomolar range. In vitro stability specificity was confirmed mammalian cells by enzyme reconstitution, transcriptional activation using combination DNA-binding domain, cellular-enzyme-activity based on...
DNA Polymerases generate pyrophosphate every time they catalyze a step of elongation. This elongation reaction is generally believed as thermodynamically favoured by the hydrolysis pyrophosphate, catalyzed inorganic pyrophosphatases. However, specific action pyrophosphatases coupled to replication in vivo was never demonstrated. Here we show that Polymerase-Histidinol-Phosphatase (PHP) domain Escherichia coli Polymerase III α subunit features pyrophosphatase activity. We also this activity...
Abstract Conformational change of proteins in response to chemical or physical signals is the underlying principle many regulatory and transport mechanisms biological systems. The ability design conformational state which can be precisely reversibly controlled would facilitate development molecular machines tailored for specific applications. Here we explore metal‐binding site engineer a peptide‐based switch called SwitCCh that assembles into homodimeric coiled‐coil addition Zn II ions low...
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...
The function of many channels and transporters is enriched by the conformational plasticity intrinsically disordered regions (IDRs). Copper transporter 1 (Ctr1) main entry point for Cu(I) ions in eukaryotes contains IDRs both at its N-terminal (Nterm) C-terminal ends. former delivers copper from extracellular matrix to selectivity filter Ctr1 lumen. However, molecular mechanism this process remains elusive due Nterm's nature. Here, we combine advanced dynamics simulations circular dichroism...
Abstract The interaction between avidin and its counterpart biotin is one of central importance in biology has been reproposed studied at length. However, the binding pocket prone to promiscuous binding, able accommodate even non‐biotinylated ligands. Comprehending factors that distinguish extremely strong with other ligands an important step fully picture thermodynamics these low‐affinity complexes. Here, we present complex chicken white egg theophylline (TEP), xanthine derivative used...
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...
Abstract Coiled-coil (CC) dimer-forming peptides are attractive designable modules for mediating protein association. Highly stable CCs desired biological activity regulation and assay. Here, we report the design versatile applications of orthogonal CC with a dissociation constant in low nanomolar range. In vitro stability specificity was confirmed mammalian cells by enzyme reconstitution, transcriptional activation using combination DNA-binding domain, cellular-enzyme-activity based on...
A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-21969-9