A5002870553- Protein Structure and Dynamics
- Enzyme Structure and Function
- RNA and protein synthesis mechanisms
- Hippo pathway signaling and YAP/TAZ
- Photosynthetic Processes and Mechanisms
- Protein Kinase Regulation and GTPase Signaling
- Protein Tyrosine Phosphatases
- Mass Spectrometry Techniques and Applications
- Hemoglobin structure and function
- Heat shock proteins research
- Computational Drug Discovery Methods
- Cellular transport and secretion
- Virology and Viral Diseases
- Alzheimer's disease research and treatments
- Ubiquitin and proteasome pathways
- Glycosylation and Glycoproteins Research
- Cancer Genomics and Diagnostics
- Plant biochemistry and biosynthesis
- Galectins and Cancer Biology
- Endoplasmic Reticulum Stress and Disease
- Genetic Neurodegenerative Diseases
- DNA and Nucleic Acid Chemistry
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Vestibular and auditory disorders
- Chemical Synthesis and Analysis
Sapienza University of Rome
2016-2025
Istituto Pasteur
2016-2025
University of Naples Federico II
2022
Institute of Molecular Biology and Pathology
2008-2020
Vita-Salute San Raffaele University
2016-2017
University of Cambridge
2003-2016
Istituti di Ricovero e Cura a Carattere Scientifico
2016
Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele
2016
Uppsala University
2007
Hutchison/MRC Research Centre
2003-2005
Abstract Several hundred clinical trials currently explore the role of circulating tumor cell ( CTC ) analysis for therapy decisions, but assays are lacking comprehensive molecular characterization s with diagnostic precision. We therefore combined a workflow enrichment and isolation pure CTCs non‐random whole genome amplification method single cells applied it to 510 189 leukocytes 66 ‐positive breast cancer patients. defined integrity index GII identify suited by different assays, such as...
We compare the folding of representative members a protein superfamily by experiment and simulation to investigate common features in mechanisms. The homeodomain three-helical, single-domain proteins exhibits spectrum processes that spans complete transition from concurrent secondary tertiary structure formation (nucleation-condensation mechanism) sequential (framework mechanism). unifying factor their mechanisms is state for (un)folding expanded very native-like, with proportion degree...
Intrinsically disordered proteins (IDPs) and intrinsically regions (IDRs) of are very common instrumental for cellular signaling. Recently, a number studies have investigated the kinetic binding mechanisms IDPs IDRs. These results allow us to draw conclusions about energy landscape coupled folding proteins. The association rate constants cover wide range (105–109 M−1 s−1) largely governed by long-range charge–charge interactions, similarly interactions between well-folded Off-rate also...
Abstract The hydrophobic effect is a major driving force in protein folding. A complete understanding of this requires the description conformational states water and molecules at different temperatures. Towards goal, we characterise cold hot denatured by modelling NMR chemical shifts using restrained molecular dynamics simulations. detailed analysis resulting structures reveals that bulk interface form on average same number hydrogen bonds. Thus, even if proteins are ‘large’ particles (in...
A classical dogma of molecular biology dictates that the 3D structure a protein is necessary for its function. However, considerable fraction human proteome, although functional, does not adopt defined folded state under physiological conditions. These intrinsically disordered proteins tend to fold upon binding their partners with mechanism elusive experimental characterization. Indeed, many hypotheses have been put forward, functional role (if any) disorder in these denatured systems still...
Abstract Intrinsically disordered proteins often become structured upon interacting with their partners. The mechanism of this ‘folding binding’ process, however, has not been fully characterised yet. Here we present a study the folding intrinsically transactivation domain c-Myb (c-Myb) binding its partner KIX. By determining structure transition state for wild-type and three mutational variants KIX, found remarkable plasticity pathway c-Myb. To explain phenomenon, show that is templated by...
The response characteristics of neurons located in the lateral vestibular nucleus (LVN) to neck rotation at 0.026 Hz, 10 degrees peak displacement, have been investigated precollicular decerebrate cats submitted ipsilateral acute (aVN) or chronic neurectomy (cVN). On whole, 105 units were tested after aVN (i.e., during first postoperative hours) and 132 cVN full compensation postural locomotor deficits). histologically either rostroventral (rvLVN) dorsocaudal part (dcLVN) Deiters' nucleus,...
DOPA decarboxylase, the dimeric enzyme responsible for synthesis of neurotransmitters dopamine and serotonin, is involved in severe neurological diseases such as Parkinson disease, schizophrenia, depression. Binding pyridoxal-5′-phosphate (PLP) cofactor to apoenzyme thought represent a central mechanism regulation its activity. We solved structure human found it exists an unexpected open conformation: compared pig kidney holoenzyme, dimer subunits move 20 Å apart two active sites become...
In the past decade, a wealth of experimental data has demonstrated that large fraction proteins, while functional, are intrinsically disordered at physiological conditions. Many proteins (IDPs) undergo disorder-to-order transition upon binding to their biological targets, phenomenon known as induced folding. Induced folding may occur through two extreme mechanisms, namely conformational selection and after binding. Although pre-existence ordered structures in IDPs is prerequisite for...
Abstract The Envelope protein (E) is one of the four structural proteins encoded by genome SARS‐CoV and SARS‐CoV‐2 Coronaviruses. It an integral membrane protein, highly expressed in host cell, which known to have important role Coronaviruses maturation, assembly virulence. E presents a PDZ‐binding motif at its C‐terminus. One key interactors intracellular environment PDZ containing PALS1. This interaction play pathology suspected affect integrity lung epithelia. In this paper we measured...
The adaptor protein Grb2, or Growth factor receptor bound 2, possesses a pivotal role in the transmission of fundamental molecular signals cell. Despite lacking enzymatic activity, Grb2 functions as dynamic assembly platform, orchestrating intracellular through its modular structure. This study delves into energetic communication domains, focusing on folding and binding properties C-SH3 domain linked to neighboring SH2 domain. Surprisingly, while stability remain robust unaffected by...
It is controversial whether fast-folding proteins can form productive on-pathway intermediates that are more stable than the denatured state because noncovalent usually evanescent. Here, we apply classical criteria for existence of intermediates: namely, and react rapidly enough to be on pathway they isolated characterized. The folding 71-residue, mainly α-helical FF domain from human HYPA/FBP11 fulfills these criteria, as was found Im7. folds in two phases, one μs other ms time scale. An...
PDZ domains are protein adapter modules present in a few hundred human proteins. They play important roles scaffolding and signal transduction. usually bind to the C termini of their target To assess binding mechanism this interaction we have performed first in-solution kinetic study for peptides corresponding ligands. Both PDZ3 from postsynaptic density 95 PDZ2 tyrosine phosphatase L1 respective through an apparent A + B → A·B without rate-limiting conformational changes. But mutant with...
Cytochrome P450s are heme-containing proteins that catalyze the oxidative metabolism of many physiological endogenous compounds. Because their unique oxygen chemistry and key role in drug xenobiotic metabolism, particular attention has been devoted elucidating mechanism substrate recognition. In this work, we analyzed three-dimensional structures a monomeric cytochrome P450 from Saccharopolyspora erythraea, commonly called EryK, binding kinetics to its ligand, erythromycin D. Three different...