A5026650137- Photosynthetic Processes and Mechanisms
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Monoclonal and Polyclonal Antibodies Research
- RNA Research and Splicing
- Trace Elements in Health
- Glycosylation and Glycoproteins Research
- Prion Diseases and Protein Misfolding
- Crystallization and Solubility Studies
- Protein Structure and Dynamics
- Protist diversity and phylogeny
- Spectroscopy and Quantum Chemical Studies
- Bacteriophages and microbial interactions
- X-ray Diffraction in Crystallography
- Nanocluster Synthesis and Applications
- Mosquito-borne diseases and control
- Supramolecular Self-Assembly in Materials
- Molecular Sensors and Ion Detection
- Heat shock proteins research
- Immunotherapy and Immune Responses
- Electron Spin Resonance Studies
- RNA modifications and cancer
- Pneumonia and Respiratory Infections
- Hemoglobin structure and function
- Marine and coastal ecosystems
- ATP Synthase and ATPases Research
Science for Life Laboratory
2014-2024
Stockholm University
2024
IRCCS Policlinico San Donato
2022-2024
Karolinska University Hospital
2014-2023
Karolinska Institutet
2014-2023
Istituti di Ricovero e Cura a Carattere Scientifico
2023
University of Pavia
2023
Weatherford College
2023
University of Milan
2023
Policlinico San Matteo Fondazione
2023
Abstract SARS-CoV-2 enters host cells through an interaction between the spike glycoprotein and angiotensin converting enzyme 2 (ACE2) receptor. Directly preventing this presents attractive possibility for suppressing replication. Here, we report isolation characterization of alpaca-derived single domain antibody fragment, Ty1, that specifically targets receptor binding (RBD) spike, directly ACE2 engagement. Ty1 binds RBD with high affinity, occluding ACE2. A cryo-electron microscopy...
Inflammatory response induced by microglia plays a critical role in the demise of neuronal populations neuroinflammatory diseases. Although toll-like receptor 4 (TLR4) microglia's inflammatory is fully acknowledged, little known about endogenous ligands that trigger TLR4 activation. Here, we report galectin-3 (Gal3) released acts as an paracrine ligand. Gal3-TLR4 interaction was further confirmed murine model (intranigral lipopolysaccharide [LPS] injection) and human stroke subjects....
Abstract Chemokine heterodimers activate or dampen their cognate receptors during inflammation. The CXCL12 chemokine forms with the fully reduced (fr) alarmin HMGB1 a physiologically relevant heterocomplex (frHMGB1•CXCL12) that synergically promotes inflammatory response elicited by G-protein coupled receptor CXCR4. molecular details of complex formation were still elusive. Here we show an integrated structural approach frHMGB1•CXCL12 is fuzzy heterocomplex. Unlike previous assumptions,...
The Ras-GAP SH3 domain–binding proteins (G3BP) are essential regulators of the formation stress granules (SG), cytosolic aggregates and RNA that induced upon cellular stress, such as virus infection. Many viruses, including Semliki Forest (SFV), block SG induction by targeting G3BP. In this work, we demonstrate G3BP-binding motif SFV nsP3 consists two FGDF motifs, in which both phenylalanine glycine residue for binding. addition, show binding partner USP10 is also mediated an motif....
Although biofilms have been observed early in the history of microbial research, their impact has only recently fully recognized. Biofilm infections, which contribute to up 80% human are associated with common disorders, such as diabetes mellitus and poor dental hygiene, but also medical implants. The chronic infections wound caries periodontitis significantly enhance morbidity, affect quality life can aid development follow-up diseases cancer. remain challenging treat antibiotic monotherapy...
Recent findings have highlighted the role of Old World alphavirus non-structural protein 3 (nsP3) as a host defence modulator that functions by disrupting stress granules, subcellular phase-dense RNA/protein structures formed upon environmental stress. This disruption mechanism was largely explained through nsP3-mediated recruitment G3BP via two tandem FGDF motifs. Here, we present 1.9 Å resolution crystal structure NTF2-like domain G3BP-1 in complex with 25-residue peptide derived from...
The peridinin-chlorophyll a -protein (PCP) of dinoflagellates is unique among the large variety natural photosynthetic light-harvesting systems. In contrast to other chlorophyll protein complexes, soluble PCP located in thylakoid lumen, and carotenoid pigments outnumber chlorophylls. structure complex consists two symmetric domains, each with central (Chl- ) surrounded by four peridinin molecules. provides distinctive surroundings for pigment molecules, PCP, specific environment around...
The obligate intracellular parasite Toxoplasma gondii exploits cells of the immune system to disseminate. Upon infection, parasitized dendritic (DCs) and microglia exhibit a hypermigratory phenotype in vitro that has been associated with enhancing dissemination vivo mice. One unresolved question is how parasites commandeer achieve systemic by 'Trojan-horse' mechanism. By chromatography mass spectrometry analyses, we identified an orthologue 14-3-3 protein family, T. (Tg14-3-3), as mediator...
Abstract SARS-CoV-2 is the etiologic agent of COVID-19, currently causing a devastating pandemic for which pharmacological interventions are urgently needed. The virus enters host cells through an interaction between spike glycoprotein and angiotensin converting enzyme 2 (ACE2) receptor. Directly preventing this presents attractive possibility suppressing replication. Here we report isolation characterization alpaca-derived single domain antibody fragment, Ty1, that specifically targets...
The compromise between affinity and specificity in TCR-dependent targeting of HLA-restricted tumor-associated antigens presents a significant challenge developing efficacious immunotherapies. As such, T cell engagers which circumvent these limitations are particular interest. We have established process to generate bispecific Designed Ankyrin Repeat Proteins (DARPins) that simultaneously target HLA-I molecules complex with peptides CD3ϵ. High-affinity HLA-A*0201/NY-ESO1 157-165 -specific...
G3BP is the central node within stress-induced protein–RNA interaction networks known as stress granules (SGs). The SG-associated proteins Caprin-1 and USP10 bind mutually exclusively to NTF2 domain of G3BP1, promoting inhibiting SG formation, respectively. Herein, we present crystal structure G3BP1-NTF2 in complex with a Caprin-1-derived short linear motif (SLiM). interacts His-31 His-62 third NTF2-binding site outside those covered by USP10, confirmed using biochemical biophysical-binding...
Streptococcus pneumoniae is a major human pathogen, and leading cause of disease death worldwide. Pneumococcal invasive triggered by initial asymptomatic colonization the upper respiratory tract. The pneumococcal serine-rich repeat protein (PsrP) lung-specific virulence factor whose functional binding region (BR) binds to keratin-10 (KRT10) promotes biofilm formation through self-oligomerization. We present crystal structure KRT10-binding domain PsrP (BR 187–385 ) determined 2.0 Å...
Abstract The major human pathogen Streptococcus pneumoniae is a leading cause of disease and death worldwide. Pneumococcal biofilm formation within the nasopharynx leads to long-term colonization persistence host. We have previously demonstrated that capsular surface-associated pneumococcal serine rich repeat protein (PsrP), key factor for formation, binds keratin-10 (KRT10) through its microbial surface component recognizing adhesive matrix molecule (MSCRAMM)-related globular binding region...
Abstract AA amyloidosis is a systemic disease characterized by deposition of misfolded serum amyloid A protein (SAA) into cross-β in multiple organs humans and animals. occurs at high SAA levels during chronic inflammation. Prion-like transmission was reported as possible cause extreme prevalence captive animals, e.g. 70% cheetah 57–73% domestic short hair (DSH) cats kept zoos shelters, respectively. Herein, we present the 3.3 Å cryo-EM structure extracted post-mortem from kidney DSH cat...
Light-harvesting complexes have evolved into very different structures but fulfill the same function, efficient harvesting of solar energy. In these complexes, pigments are fine-tuned and properly arranged to gather incoming photons. photosynthetic dinoflagellate Amphidinium carterae, two variants soluble light-harvesting complex PCP been found [main form (MFPCP) high-salt (HSPCP)], which show small variations in their pigment arrangement tuning mechanisms. This feature makes them ideal...
Atomic layer deposition of ultrathin HfO2 on unmodified graphene from HfCl4 and H2O was investigated. Surface RMS roughness down to 0.5 nm obtained for amorphous, 30 thick hafnia film grown at 180 degrees C. deposited also in a two-step temperature process where the initial growth about 1 170 C continued up 10-30 300 This yielded uniform, monoclinic films with 1.7 10-12 2.5 films. Raman spectroscopy studies revealed that caused compressive biaxial strain whereas no extra defects were...
Systemic AA-amyloidosis is a protein-misfolding disease characterized by fibril deposition of serum amyloid-A protein (SAA) in several organs humans and many animal species. Fibril deposits originate from abnormally high levels SAA during chronic inflammation. A prevalence has been reported captive cheetahs horizontal transmission proposed. In domestic cats, mainly described predisposed breeds but only rarely short-hair cats. Aims the study were to determine dead shelter Liver, kidney,...
The murine interleukin 4 receptor (IL-4R) exists as a transmembrane protein transducing pleiotropic IL-4 functions, or soluble (s)IL-4–binding molecule with potent immunoregulatory effects. In this study we identified and characterized IL-4R allotype. Sequence analysis of the cDNA BALB/c mice revealed 18 base substitutions leading to three extracellular five cytoplasmic amino acid changes when compared published sequence C57BL/6 mice. Analyses allotype-specific mAbs that AKR/J SJL/J possess...
The triplet state of the carotenoid peridinin in refolded N-domain peridinin-chlorophyll-protein (PCP) antenna complex from Amphidinium carterae is investigated by orientation-selected pulse Q-band ENDOR spectroscopy (34 GHz). created triplet−triplet transfer 3Chl a, generated illumination at 630 nm. lifetimes are close to minimum duration experiment (∼10 μs). Thirteen proton hyperfine coupling (hfc) tensors deduced for state. Additionally, density functional theory (DFT) calculations...
The peridinin–chlorophyll a ‐protein (PCP) from dinoflagellates is soluble light harvesting antenna which gathers incoming photons mainly by the carotenoid peridinin. In PCPs reconstituted with different chlorophylls, peridinin to chlorophyll energy transfer rates are well predicted Förster‐like theory, but only if pigment arrangements identical in all PCPs. We have determined X‐ray structures of Chlorophyll‐ b (Chl‐ ), d ) and Bacteriochlorophyll‐ (BChl‐ resolutions ⩽2 Å. three cases...