A5010826630- Protein Structure and Dynamics
- Enzyme Structure and Function
- Surfactants and Colloidal Systems
- Bacterial Genetics and Biotechnology
- Electrostatics and Colloid Interactions
- RNA Interference and Gene Delivery
- Protein Interaction Studies and Fluorescence Analysis
- Bacteriophages and microbial interactions
- Nitric Oxide and Endothelin Effects
- Signaling Pathways in Disease
- Microtubule and mitosis dynamics
- RNA modifications and cancer
- Supramolecular Chemistry and Complexes
- Immunotherapy and Immune Responses
- DNA and Nucleic Acid Chemistry
- Supramolecular Self-Assembly in Materials
- Cancer-related Molecular Pathways
- Spectroscopy and Quantum Chemical Studies
- Protease and Inhibitor Mechanisms
- Microbial Community Ecology and Physiology
- RNA Research and Splicing
- Phosphodiesterase function and regulation
- Cancer therapeutics and mechanisms
- Cholinesterase and Neurodegenerative Diseases
- Geophysics and Gravity Measurements
Foundation for Research and Technology Hellas
2018-2023
FORTH Institute of Molecular Biology and Biotechnology
2018-2023
SPring-8
2011-2019
Japan Synchrotron Radiation Research Institute
2011-2019
RIKEN
2014
European Molecular Biology Laboratory
2006-2009
European Molecular Biology Laboratory
2008
Institut de Biologie Structurale
2007-2008
Russian Academy of Sciences
2007-2008
Université Joseph Fourier
2007-2008
Structural analysis of flexible macromolecular systems such as intrinsically disordered or multidomain proteins with linkers is a difficult task high-resolution techniques are barely applicable. A new approach, ensemble optimization method (EOM), proposed to quantitatively characterize in solution using small-angle X-ray scattering (SAXS). The flexibility taken into account by allowing for the coexistence different conformations protein contributing experimental pattern. These conformers...
Proteins with intrinsically disordered domains are implicated in a vast range of biological processes, especially cell signaling and regulation. Having solved the quaternary structure folded tumor suppressor p53 by multidisciplinary approach, we have now determined average ensemble N-terminal transactivation domain (TAD) using residual dipolar couplings (RDCs) from NMR spectroscopy small-angle x-ray scattering (SAXS). Remarkably, not only were able to measure RDCs isolated TAD, but also do...
One of the most important overall parameters, which can be derived from small-angle X-ray scattering (SAXS) experiments on macromolecular solutions is molecular mass (MM) solute. In particular, for a monodisperse protein solution, MM solute calculated extrapolated intensity at zero angle I(0). Assessing by SAXS provides valuable information about oligomeric state and absence unspecific aggregation in solution. The value either estimated comparison with standard known or determining absolute...
Tau is one of the two main proteins involved in pathology Alzheimer's disease via formation β-sheet rich intracellular aggregates named paired helical filaments (PHFs). Given that tau a natively unfolded protein with no folded core (even upon binding to physiological partners such as microtubules), its structural analysis by high-resolution techniques has been difficult. In this study, employing solution small-angle X-ray scattering from full length isoforms and variety deletion point...
The homotetrameric tumor suppressor p53 consists of folded core and tetramerization domains, linked flanked by intrinsically disordered segments that impede structure analysis x-ray crystallography NMR. Here, we solved the quaternary human in solution a combination small-angle scattering, which defined its shape, NMR, identified domain interfaces showed domains had same intact protein as fragments. We combined data with electron microscopy on immobilized samples provided medium resolution 3D...
In colloidal systems, the interplay between short range attraction and long-range repulsion can lead to a low density associated state consisting of clusters individual particles. Recently, such an equilibrium cluster phase was also reported for concentrated solutions lysozyme at ionic strength close physiological pH. Stradner et al. [(2004) Equilibrium formation in protein colloids. Nature 432:492-495] found that position low-angle interference peak small-angle x-ray neutron scattering...
The proteolytic activity of matrix metalloproteinases toward extracellular components (ECM), cytokines, chemokines, and membrane receptors is crucial for several homeostatic pathological processes. Active MMPs are a family single-chain enzymes (23 members in the human genome), most which constituted by catalytic domain hemopexin-like connected linker. X-ray structures MMP-1 MMP-2 suggest conserved well-defined spatial relationship between two domains. Here we present structural data MMP-12,...
Polymeric micelles have been extensively studied as nanoscale drug carriers. Knowing the inner structure of polymeric that encapsulate hydrophobic drugs is important to design effective In our study, compound tetrabromocathecol (TBC) was chosen a drug-equivalent model molecule. The bromine atoms in TBC act probes anomalous small-angle X-ray scattering (ASAXS) allowing for its localization whose shape and size were determined by normal (SAXS). Light measurements coupled with field flow...
Abstract The concept of micelles was first proposed in 1913 by McBain and has rationalized numerous experimental results the self-aggregation surfactants. It is generally agreed that aggregation number ( N agg ) for spherical no exact value a certain distribution. However, our studies calix[4]arene surfactants showed they were monodisperse with defined whose values are chosen from 6, 8, 12, 20, 32. Interestingly, some these numbers coincide face Platonic solids, thus we named them “Platonic...
The microtubule-associated protein (MAP)/microtubule affinity regulating kinase (MARK)/Par-1 phosphorylates proteins tau, MAP2, and MAP4 is involved in the regulation of microtubule-based transport. Par-1, a homologue MARK Drosophila Caenorhabditis elegans, essential for development embryonic polarity. Four isoforms are found humans. Recently, we reported crystal structure catalytic ubiquitin-associated domains MARK2, an isoform enriched brain (Panneerselvam, S., Marx, A., Mandelkow, E.-M.,...
A series of cationic calix[4]arene-based lipids with alkyl chains varying length were newly synthesized, and the ones propyl hexyl tails, denoted by CaL[4]C3 C6, respectively, found to form spherical micelles at low pH (protonated state amine headgroup). Upon deprotonation increasing pH, showed a sphere-to-cylinder transition, while CaL[4]C6 changed from sphere, cylinder, monolayer vesicle. Synchrotron small-angle X-ray scattering (SAXS) patterns both cylindrical exhibited sharp intensity...
An amphiphilic macrocycle based on pillar[5]arene with polar lysine head groups spontaneously self-assembles into a bimolecular micelle in water. This self-assembled structure was characterized by small angle X-ray scattering (SAXS), field flow fluctuation coupled multi-angle light (FFF-MALS) and atomic force microscopy (AFM). The self-assembly of dimeric spherical micelles represents new molecular architecture for formation.
Abstract: To determine whether monoclonal/oligoclonal T cells are present in abdominal aortic aneurysm (AAA) lesions, we amplified β‐chain cell receptor (TCR) transcripts from these lesions by the nonpalindromic adaptor (NPA)‐polymerase chain reaction (PCR)/V‐β‐specific PCR followed cloning and sequencing. Sequence analysis revealed presence of substantial proportions identical TCR AAA 9 10 patients examined, strongly suggesting oligoclonal populations αβ TCR+ cells. We have also shown γδ...
The full-length, two-domain response regulator RegX3 from Mycobacterium tuberculosis is a dimer stabilized by three-dimensional domain swapping. Dimerization known to occur in the OmpR/PhoB subfamily of regulators upon activation but has previously only been structurally characterized for isolated receiver domains. bipartite intermolecular interface, which buries 2357 A(2) per monomer. two parts interface are between domains (dimerization interface) and composite effector second molecule...
Recurrent protein folding motifs include various types of helical bundles formed by α-helices that supercoil around each other. While specific patterns amino acid residues (heptad repeats) characterize the highly versatile motif four-α-helical bundles, significance polypeptide chain directionality is not sufficiently understood, although it determines sequence patterns, dipoles, and other parameters for oligomerization processes bundles. To investigate aspects in sequence-structure...
Bacterial Type III Secretion Systems (T3SSs) are specialized multicomponent nanomachines that mediate the transport of proteins either to extracellular locations or deliver effectors directly into eukaryotic host cell cytoplasm. Shigella , causing agent bacillary dysentery shigellosis, bears a set T3SS termed translocators form pore in membrane. IpaB, major translocator system, is key factor promoting pathogenicity. Prior secretion, IpaB maintained inside bacterial cytoplasm secretion...
We carried out synchrotron X-ray scattering experiments from four DNA supermolecules designed to form tetrapod shapes; these had different sequences but identical numbers of total base pairs, and each contained an immunostimulatory CpG motif. confirmed that the did indeed expected shape. The sample largest radius gyration (Rg) induced most cytokine secretion cultured immune cells. Structural analysis in combination with a rigid model atomic scale revealed larger Rg can be ascribed...
ABSTRACT Many plant-pathogenic bacteria of considerable economic importance rely on type III secretion systems (T3SSs) the Hrc-Hrp 1 family to subvert their plant hosts. T3SS gene expression is regulated through HrpG and HrpV proteins, while controlled by gatekeeper HrpJ. A link between two mechanisms was so far unknown. Here, we show that a mechanistic coupling exists cascades direct binding HrpG/HrpV heterodimer, acting as chaperone, The ternary complex docked cytoplasmic side inner...
Determining changes in the composition of cell populations is made possible by technologies like single-cell transcriptomics, CyTOF, and microbiome sequencing. However, existing methods for differential abundance do not model some ...Cellular omics such as genomics, proteomics, microbiomics allow characterization tissue microbial community composition, which can be compared between conditions to identify biological drivers. This strategy has been critical ...
We have recently introduced the concept of "Platonic micelles", preference spherical micelles to specific aggregation numbers mostly coinciding with number faces platonic solids. This effect was observed on bulky, calix[4]arene-based surfactant systems small numbers. The preferred result in better sphere coverage, highliting packing and "protection" hydrophobic cores from aqueous solvent as most important factor for this preference. In present study we further explore interactions that drive...
Soluble guanylate cyclase (sGC) regulates numerous physiological processes. The β subunit Heme Nitric Oxide/Oxygen (HNOX) domain makes this protein sensitive to small gaseous ligands. structural basis of the activation mechanism sGC under influence ligands (NO, O₂, CO) is poorly understood. We examine effect different on human HNOX domain. systems with were generated and explored using Molecular Dynamics (MD). distance between heme Fe
Abstract In the nitric oxide (NO) signaling pathway, human soluble guanylate cyclase ( h sGC) synthesizes cyclic guanosine monophosphate (cGMP); responsible for regulation of cGMP-specific protein kinases (PKGs) and phosphodiesterases (PDEs). The crystal structure inactive sGC dimer is known, but there still a lack information regarding substrate-specific internal motions that are essential catalytic mechanism hs GC. current study, GC heterodimer complexed with triphosphate (GTP) cGMP was...