A5002422109- Protein Structure and Dynamics
- Supramolecular Self-Assembly in Materials
- Alzheimer's disease research and treatments
- Neuroendocrine regulation and behavior
- Stress Responses and Cortisol
- Memory and Neural Mechanisms
- Enzyme Structure and Function
- Lipid Membrane Structure and Behavior
- Chemical Synthesis and Analysis
- Machine Learning in Bioinformatics
- Receptor Mechanisms and Signaling
- Proteins in Food Systems
- RNA and protein synthesis mechanisms
- Glycosylation and Glycoproteins Research
- Protein purification and stability
- DNA and Nucleic Acid Chemistry
- Bioinformatics and Genomic Networks
- Photoreceptor and optogenetics research
- S100 Proteins and Annexins
- Spectroscopy and Quantum Chemical Studies
- Retinal Development and Disorders
- Neurobiology and Insect Physiology Research
- Prion Diseases and Protein Misfolding
- Nanocluster Synthesis and Applications
- Zebrafish Biomedical Research Applications
Mossakowski Medical Research Institute, Polish Academy of Sciences
2021-2024
Polish Academy of Sciences
2019-2024
Institute of High Pressure Physics
2019-2022
University of Warsaw
2012-2018
International Institute of Molecular and Cell Biology
2009-2010
The γ-secretase complex has a decisive role in the development of Alzheimer’s disease, that it cleaves precursor to create amyloid β peptide whose aggregates form senile plaques encountered brains patients. Γ-secretase is member intramembrane-cleaving proteases which process their transmembrane substrates within bilayer. Many mutations early onset familial disease are linked presenilin 1, catalytic component γ-secretase, active requires its endoproteolytic cleavage into N-terminal and...
The CABS coarse-grained model is a well-established tool for modeling globular proteins (predicting their structure, dynamics, and interactions). Here we introduce an extension of the representation force field (CABS-membrane) to effect biological membrane environment on structure proteins. We validate CABS-membrane in folding simulations 10 short helical not using any knowledge about structure. start from random protein conformations placed outside allow full flexibility modeled during...
Insulin aggregation poses a significant problem in pharmacology and medicine as it occurs during prolonged storage of the hormone vivo at insulin injection sites. We have recently shown that dominant forces driving self-assembly fibrils are likely to arise from intermolecular interactions involving N-terminal segment A-chain (ACC1–13). Here, we study how proline substitutions within pilot GIVEQ sequence this fragment affect its propensity aggregate both neutral acidic environments. In...
Rhodopsin is palmitylated at two cysteine residues in its carboxyl terminal region. We have looked the effects of palmitylation on molecular interactions formed by rhodopsin using single-molecule force spectroscopy and function both vitro vivo approaches. A knockin mouse model expressing palmitate-deficient was used for live animal studies to obtain native tissue samples assays. specifically chromophore-binding pocket, with transducin, stabilizing receptor structure. The structure largely...
The Formyl Peptide Receptor 1 (FPR1) is an important chemotaxis receptor involved in various aspects of host defense and inflammatory processes. We constructed a model FPR1 using as novel template the chemokine CXCR4 from same branch phylogenetic tree G-protein-coupled receptors. previously employed rhodopsin contained bulge at extracellular part TM2 which directly influenced binding ligands. also conducted molecular dynamics (MD) simulations apo form well complexed with agonist fMLF...
Poly-l-glutamic acid (PLGA) forms amyloid-like β2-fibrils with the main spectral component of vibrational amide I′ band unusually shifted below 1600 cm–1. This distinct infrared feature has been attributed to presence bifurcated hydrogen bonds coupling C═O and N–D (N–H) groups chains glutamate side chains. Here, we investigate how decreasing chain length PLGA affects its capacity form β2-fibrils. A series acidified aqueous solutions synthetic (l-Glu)n peptides (n ≈ 200, 10, 6, 5, 4, 3) were...
Bovine serum albumin (BSA) is often employed as a proteinaceous component for synthesis of luminescent protein-stabilized gold nanoclusters (AuNC): intriguing systems with many potential applications. Typically, the formation BSA-AuNC conjugate occurs under strongly alkaline conditions. Due to sheer complexity intertwined chemical and structural transitions taking place upon formation, state enveloping AuNCs remains poorly characterized. Here, we study conformational properties BSA bound...
The CABS model can be applied to a wide range of protein-protein and protein-peptide molecular modeling tasks, such as simulating folding pathways, predicting structures, docking, analyzing the structural dynamics complexes. In this work, we use CABS-dock tool in two diverse tasks: 1) structures amyloid protofilaments 2) identifying cleavage sites peptide substrates proteolytic enzymes. first case, simulations simultaneous docking amyloidogenic peptides indicated that accurately predict...
Chain-length polydispersity is among the least understood factors governing fibrillation propensity of homopolypeptides. For monodisperse poly-L-glutamic acid (PLGA), tendency to form fibrils depends main-chain length. Long-chained PLGA, so-called (Glu)200, fibrillates more readily than short (Glu)5 fragments. Here we show that conversion α-helical (Glu)200 into amyloid-like β-fibrils dramatically accelerated in presence intrinsically disordered (Glu)5. While separately self-assembled and...
ATP acts as a biological hydrotrope preventing protein aggregation. Here, we report novel chimeric peptide, ACC1-13K8, with an unusual capacity to bind and incorporate while self-assembling into amyloid fibrils. The amino acid sequence combines highly amyloidogenic segment of insulin's A-chain (ACC1-13) octalysine (K8). Fibrillization requires binding 2 molecules per ACC1-13K8 monomer is not triggered by adenosine di- monophosphates (ADP, AMP). Infrared CD spectra AFM-based morphological...
Rats are believed to communicate their emotional state by emitting two distinct types of ultrasonic vocalizations. The first is long “22-kHz” vocalizations (>300 ms, <32 kHz) with constant frequency, signaling aversive states and the second, short “50-kHz” calls (<150 >32 kHz), often frequency-modulated, in appetitive situations. Here we describe a new-type emitted at higher pitch Wistar spontaneously hypertensive rats (SHR) an intensified – prolonged fear conditioning. These...
β-adrenergic receptors (βARs) belong to a key molecular targets that regulate the most important processes occurring in human organism. Although over last decades zebrafish model has been developed as complementary rodents biomedical research, role of β2AR regulation pathological and toxicological effects remains elucidate. Therefore, study aimed clarify with particular emphasis on distinct subtypes A B β2AR. As compounds selective agonists – (R,R)-fenoterol ((R,R)-Fen) its new derivatives:...
Conformational transitions involving aggregated proteins or peptides are of paramount biomedical and biotechnological importance. Here, we report an unusual freeze-induced structural reorganization within a β-sheet-rich ionic coaggregate poly(l-lysine), PLL, poly(l-glutamic acid), PLGA. Freezing aqueous suspensions the PLL–PLGA β-aggregate in presence low concentrations salt (NaBr) induces instantaneous β-sheet-to-disorder transition, as probed by infrared spectroscopy amide I′ band region....
Conformational transitions of globular proteins into amyloid fibrils are complex multistage processes exceedingly challenging to simulate using molecular dynamics (MD). Slow monomer diffusion rates and rugged free energy landscapes disfavor swift self-assembly orderly architectures within timescales accessible all-atom MD. Here, we conduct a multiscale MD study the amyloidogenic insulin: small protein with topology defined by two polypeptide chains interlinked three disulfide bonds. To avoid...
Rats are believed to communicate their emotional state by emitting two distinct types of ultrasonic vocalizations. The first is long ‘22-kHz’ vocalizations (>300 ms, <32-kHz) with constant frequency, signaling aversive states, and the second short ‘50-kHz’ calls (<150 >32 kHz), often frequency-modulated, in appetitive situations. Here, we describe emitted at a higher pitch male Wistar spontaneously hypertensive rats (SHR) an intensified – prolonged fear conditioning. These calls,...
Canonical amyloid fibrils are composed of covalently identical polypeptide chains. Here, we employ kinetic assays, atomic force microscopy, infrared spectroscopy, circular dichroism, and molecular dynamics simulations to study fibrillization patterns two chimeric peptides, ACC1–13E8 ACC1–13K8, in which a potent amyloidogenic stretch derived from the N-terminal segment insulin A-chain (ACC1–13) is coupled octaglutamate or octalysine segments, respectively. While large electric charges prevent...
Rats are believed to communicate their emotional state by emitting two distinct types of ultrasonic vocalizations. The first is long “22-kHz” vocalizations (>300 ms, <32 kHz) with constant frequency, signaling aversive states and the second, short “50-kHz” calls (<150 >32 kHz), often frequency-modulated, in appetitive situations. Here we describe emitted at a higher pitch male Wistar spontaneously hypertensive rats (SHR) an intensified – prolonged fear conditioning. These calls,...