A5014858250- Protein Structure and Dynamics
- Alzheimer's disease research and treatments
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Enzyme Structure and Function
- DNA and Nucleic Acid Chemistry
- Signaling Pathways in Disease
- Microbial metabolism and enzyme function
- Glycosylation and Glycoproteins Research
- Erythrocyte Function and Pathophysiology
- NMR spectroscopy and applications
- Advanced MRI Techniques and Applications
- ATP Synthase and ATPases Research
- Metabolomics and Mass Spectrometry Studies
- Diabetes and associated disorders
- Blood properties and coagulation
- Mass Spectrometry Techniques and Applications
- Polyamine Metabolism and Applications
- Prion Diseases and Protein Misfolding
- Metal complexes synthesis and properties
- Trace Elements in Health
- Spectroscopy and Quantum Chemical Studies
- Protein Interaction Studies and Fluorescence Analysis
- Protein Kinase Regulation and GTPase Signaling
- Redox biology and oxidative stress
- Amino Acid Enzymes and Metabolism
Istituto Nazionale Biostrutture e Biosistemi
2010-2024
University of Udine
2015-2024
Universidade Federal de Mato Grosso do Sul
2021
University College London
2017-2020
University of Padua
1992-2004
University of Trento
1999
University of Edinburgh
1997
Birkbeck, University of London
1996-1997
University of Bologna
1992
Systemic amyloidosis is a usually fatal disease caused by extracellular accumulation of abnormal protein fibers, amyloid fibrils, derived misfolding and aggregation soluble globular plasma precursors. Both WT genetic variants the normal transthyretin (TTR) form amyloid, but neither leading to fibrillogenesis nor anatomical localization TTR deposition are understood. We have previously shown that, under physiological conditions, trypsin cleaves human in mechano-enzymatic mechanism that...
Abstract The solution structure of human β2‐microglobulin (β2‐m), the nonpolymorphic component class I major histocompatibility complex (MHC‐I), was determined by 1 H NMR spectroscopy and restrained modeling calculations. Compared to previous structural data obtained from secondary isolated protein crystal MHC‐I, in which is associated heavy‐chain component, several differences are observed. most important rearrangements were observed for (1) strands V VI (loss C‐terminal N‐terminal end,...
Dialysis-related amyloidosis is characterized by the deposition of insoluble fibrils ofβ2-microglobulin (β2-m) in musculoskeletal system. Atomic force microscopy inspection ex vivo amyloid material reveals presence bundles often associated to collagen fibrils. Aggregation experiments were undertaken vitro with aim reproducing physiopathological fibrillation process. To this purpose, atomic microscopy, fluorescence techniques, and NMR employed. We found that temperature pH conditions similar...
The tripeptide glutathione (γ‐L‐Glu‐L‐Cys‐Cly, GSH) is an important intracellular reducing agent for Cu(II) and complexation Cu(I). We have studied the of Cu(I) to GSH in aqueous solution at a range pH values Cu(I):GSH molar ratios by 1 H‐NMR 13 C‐NMR spectroscopy X‐ray absorption spectroscopy. NMR data are consistent with formation complex approximate 1:1 stoichiometry [Cu(SG)] as major species only thiolate sulfur binding rate exchange GS‐Cu was determined be s ‐1 283 K, 6.8. spectroscopic...
The discovery of methods suitable for the conversion in vitro native proteins into amyloid fibrils has shed light on molecular basis amyloidosis and provided fundamental tools drug discovery. We have studied capacity a small library tetracycline analogues to modulate formation or destructuration β2-microglobulin fibrils. inhibition fibrillogenesis wild type protein was first established presence 20% trifluoroethanol confirmed under more physiologic environment including heparin collagen....
Abstract Aggregation of the amyloid‐β peptide (Aβ) into fibrillar structures is a hallmark Alzheimer's disease. Thus, preventing self‐assembly Aβ an attractive therapeutic strategy. Here, we used experimental techniques and atomistic simulations to investigate influence carnosine, dipeptide naturally occurring in brain, on aggregation. Scanning force microscopy, circular dichroism thioflavin T fluorescence experiments showed that carnosine does not modify conformational features Aβ42 but...
Nanoparticles (NPs) are known to exhibit distinct physical and chemical properties compared with the same materials in bulk form. NPs have been repeatedly reported interact proteins, this interaction can be exploited affect processes undergone by such as fibrillogenesis. Fibrillation is common many living organisms, it causes tissue-specific or systemic amyloid diseases. The nature of their surface chemistry crucial assessing affinity for proteins effects on them. Here we present first...
Abstract Motivation: Electrostatic calculations are an important tool for deciphering many functional mechanisms in proteins. Generalized Born (GB) models offer a fast and convenient computational approximation over other implicit solvent-based electrostatic models. Here we present novel GB-based web server, using the program Bluues, to calculate numerous features including pKa-values surface potentials. The output is organized allowing both experts beginners rapidly sift data. A feature of...
AL amyloidosis is a life-threatening disease caused by deposition of immunoglobulin light chains. Whilst the mechanisms underlying chains amyloidogenesis in vivo remain unclear, several studies have highlighted role that tissue environment and structural amyloidogenicity individual pathogenesis.AL natural deposits contain both full-length fragments encompassing variable domain (VL) as well different length segments constant region (CL), thus highlighting relevance proteolysis may...
The Poisson-Boltzmann (PB) equation and its linear approximation have been widely used to describe biomolecular electrostatics. Generalized Born (GB) models offer a convenient computational for the more fundamental approach based on equation, allows estimation of pairwise contributions electrostatic effects in molecular context.We implemented single program most common analyses properties proteins. first computes generalized radii, via surface integral then it uses radii (using finite radius...
Abstract A wide range of human diseases is associated with mutations that, destabilizing proteins native state, promote their aggregation. However, the mechanisms leading from folded to aggregated states are still incompletely understood. To investigate these mechanisms, we used a combination NMR spectroscopy and molecular dynamics simulations compare state Beta-2 microglobulin (β2m), whose aggregation dialysis-related amyloidosis, its aggregation-resistant mutant W60G. Our results indicate...
β2-microglobulin (β2m), the light chain of class I major histocompatibility complex, is responsible for dialysis-related amyloidosis and, in patients undergoing long term dialysis, full-length and chemically unmodified β2m converts into amyloid fibrils. The protein, belonging to immunoglobulin superfamily, common other members this family, experiences during its folding a long-lived intermediate associated trans-to-cis isomerization Pro-32 that has been addressed as precursor fibril...
Detailed studies of the kinetics platination single‐stranded 14‐base DNA oligonucleotide d(ATACATGGTACATA) and corresponding duplex by cis ‐[Pt(NH 3 ) 2 (H O) ] 2+ show that HPLC NMR are complementary methods which provide similar results. The 5'‐G 3'‐G monofunctional intermediates were trapped, separated characterized (via 15 NH labeling) enzymatic digestion followed mass spectrometry. kinetic data compared with those for reactions ‐[PtCl (NH (cisplatin) its monohydrolysed analogue. For...
Three variants of human beta(2)-microglobulin (beta(2)-m) were compared with wild-type protein. For two variants, namely the mutant R3Abeta(2)-m and form devoid N-terminal tripeptide (DeltaN3beta(2)-m), a reduced unfolding free energy was measured beta(2)-m, whereas an increased stability observed for H31Ybeta(2)-m. The solution structure could be determined by (1)H NMR spectroscopy restrained modeling only that showed same conformation as parent species, except deviations at interstrand...
It has been claimed that beta2-microglobulin (beta2-m) interacts with type I and II collagen, this property linked to the tissue specificity of beta2-m amyloid deposits target osteo-articular system. The binding parameters interaction between collagen were determined by band shift electrophoresis surface plasma resonance using bovine various isoforms beta2-m. Wild-type binds a Kd 4.1 x 10(-4) M 2.3 10(-3) M. By BIAcore system we monitored properties conformers slow phase folding...
Dissociation of the native transthyretin (TTR) tetramer is widely accepted as critical step in TTR amyloid fibrillogenesis. It modelled by exposure protein to non-physiological low pH vitro and inhibited small molecule compounds, such drug tafamidis. We have recently identified a new mechano-enzymatic pathway fibrillogenesis vitro, catalysed selective proteolytic cleavage, which produces high yield genuine fibrils. This efficiently only ligands that occupy both binding sites TTR. Tolcapone,...
Estimation of configurational entropy from molecular dynamics trajectories is a difficult task which often performed using quasi-harmonic or histogram analysis. An entirely different approach, proposed recently, estimates local density distribution around each conformational sample by measuring the distance its nearest neighbors. In this work we show theoretically well grounded method can be easily applied to estimate sampling. We consider set systems that are representative important...
Entropy calculation is an important step in the postprocessing of molecular dynamics trajectories or predictive models. In recent years nearest neighbor method has emerged as a powerful to deal flexible way with dimensionality problem. Here we provide two programs, PBD2ENTROPY and PDB2TRENT that compute conformational translational–rotational entropy, respectively, based on method. PDB2ENTROPY takes input files containing following: (1) ensembles same molecule(s) PDB format (2) definitions...
Protein aggregation including the formation of dimers and multimers in solution, underlies an array human diseases such as systemic amyloidosis which is a fatal disease caused by misfolding native globular proteins damaging structure function affected organs. Different kind interactors can interfere with protein solution. A very special class are nanoparticles thanks to extremely efficient extension their interaction surface. In particular citrate-coated gold (cit-AuNPs) were recently...
The wild type protein, transthyretin (TTR), and over 120 genetic TTR variants are amyloidogenic cause, respectively, sporadic hereditary systemic amyloidosis. homotetrameric contains two identical thyroxine binding pockets, occupation of which by specific ligands can inhibit amyloidogenesis in vitro. Ligand stabilizes the tetramer, inhibiting its proteolytic cleavage dissociation. Here, we show with solution-state NMR that ligand induces long-distance conformational changes have not...
The structure of AcP from the hyperthermophilic archaeon Sulfolobus solfataricus has been determined by (1)H-NMR spectroscopy and X-ray crystallography. Solution crystal structures (1.27 A resolution, R-factor 13.7%) were obtained on full-length protein an N-truncated form lacking first 12 residues, respectively. overall Sso fold, starting at residue 13, displays same betaalphabetabetaalphabeta topology previously described for other members family mesophilic sources. unstructured N-terminal...