@article{SCOPUS_ID:105033505349,

title = {Exploring proteins and protein–ligand complexes through residue interaction networks},

author = {Sol C. Begue and Emanuela Leonardi and Giovanni Minervini and Silvio C. E. Tosatto},

url = {https://www.scopus.com/record/display.uri?eid=2-s2.0-105033505349&origin=inward},

doi = {10.1038/s41596-026-01334-0},

year  = {2026},

date = {2026-01-01},

journal = {Nature Protocols},

publisher = {Springer Nature},

abstract = {© Springer Nature Limited 2026.Protein structures provide a wealth of information regarding biological functions and underlying mechanisms. The growing availability of high-quality structure predictions and extended molecular simulations has further expanded the potential to leverage these data in a myriad of different ways. Yet, an abundance of data can obscure important information, making it difficult to focus on biologically relevant features. Residue interaction networks (RINs) address this challenge by condensing structural data into subsets of well-defined noncovalent molecular interactions. In this Protocol, we explore how the RIN generator (RING) software can be used to gain biological insights by constructing detailed RINs for proteins and protein–ligand complexes. We provide a step-by-step guide to performing both single- and multi-state protein analyses using the RING web server and a stand-alone software package. In addition, we include a dedicated procedure for sequential multi-file analysis, which can be performed exclusively through the command-line interface. All potential inputs and outputs are explained in detail, along with strategies for downstream data processing. Designed for researchers in biology and related fields with minimal or no programming experience, the entire workflow can be completed in <45 min.},

note = {Cited by: 0},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{SCOPUS_ID:105027149057,

title = {Desmoplakin Cardiomyopathy: Gene Dose-Dependent Myocardial Remodeling, Arrhythmias, and Premature Death},

author = {Anna Guazzo and Induja Perumal Vanaja and Anna Di Bona and Riccardo Bariani and Maria C. Disalvo and Mattia Albiero and Nicolas Kuperwasser and Pierre David and Rudy Celeghin and Vittoria Di Mauro and Arianna Scalco and María López-Moreno and Marco Cason and Monica De Gaspari and Mila Della Barbera and Stefania Rizzo and Laura Ventura and Domenico Corrado and Barbara Bauce and Giuseppe Zanotti and Gaetano Thiene and Kalliopi Pilichou and Giovanni Minervini and José Maria Perez Pomares and Mario Pende and Cristina Basso and Marco Mongillo and Tania Zaglia},

url = {https://www.scopus.com/record/display.uri?eid=2-s2.0-105027149057&origin=inward},

doi = {10.1016/j.jacep.2025.10.031},

year  = {2026},

date = {2026-01-01},

journal = {JACC: Clinical Electrophysiology},

publisher = {Elsevier Inc.},

abstract = {© 2025 The AuthorsBackground: Pathogenic variants in DSP cause arrhythmogenic cardiomyopathies with variable inheritance pattern. Recessive mutations underlie syndromic forms such as Carvajal syndrome, whereas dominant variants cause DSP cardiomyopathy, a left-dominant arrhythmogenic cardiomyopathy characterized by early electrical instability, inflammation, and fibrosis. The mechanisms driving these phenotypes remain poorly defined. Objectives: The authors sought to create a clinically relevant platform to investigate disease mechanisms in Desmoplakin Cardiomyopathy. Methods: We generated a knock-in mouse carrying the DspS311A mutation, orthologous to the human pathogenic hotspot S299R. Heterozygous and homozygous mice (n ≥6/group) were longitudinally phenotyped by echocardiography, electrocardiographic telemetry, histology, and ultrastructural and molecular analyses. Moderate treadmill exercise was used as a physiological stressor. Outcomes included cardiac function, arrhythmias, fibrosis, apoptosis, inflammation, and desmosomal integrity. Results: Homozygous DspS311A/S311A mice developed early biventricular dysfunction with subepicardial necrosis, replacement fibrosis, myocardial inflammation, spontaneous arrhythmias, and cutaneous defects, recapitulating Carvajal syndrome. Heterozygous DspWT/S311A mice exhibited hallmarks of dominant DSP cardiomyopathy: patchy left ventricular fibrosis, apoptosis, inflammation, and electrical instability preceding systolic impairment. Desmosomal remodeling occurred in both genotypes, with connexin-43 mislocalization evident from 1 month, whereas β-catenin nuclear translocation and reduced DSP/DSG2 protein were restricted to homozygotes. Of note, spontaneous arrhythmias and electrical instability were already present in both genotypes, temporally preceding structural remodeling. Exercise accelerated apoptosis, fibrosis, arrhythmias, and premature death. Conclusions: This DspS311A knock-in model captures key aspects of recessive and dominant DSP cardiomyopathies, uniquely combining spontaneous arrhythmias, inflammation, and extracardiac features. This model provides a unique in vivo platform to dissect DSP-related arrhythmogenic mechanisms and to test therapies aimed at preventing sudden cardiac death.},

note = {Cited by: 1; Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{SCOPUS_ID:105018034228,

title = {Mathematical modeling and simulation of tumor-induced angiogenesis in retinal hemangioblastoma},

author = {Franco Pradelli and Giovanni Minervini and Pradeep Venkatesh and Shorya Azad and Hector Gomez and Silvio C. E. Tosatto},

url = {https://www.scopus.com/record/display.uri?eid=2-s2.0-105018034228&origin=inward},

doi = {10.1371/journal.pcbi.1012799},

year  = {2025},

date = {2025-01-01},

journal = {PLOS Computational Biology},

volume = {21},

number = {9},

publisher = {Public Library of Science},

abstract = {Copyright: © 2025 Pradelli et al. This is an open access article distributed under the terms of the Creative Commons Attribution LicenseRetinal Hemangioblastoma (RH) is the most frequent manifestation of the von Hippel-Lindau syndrome (VHL), a rare disease associated with the germline mutation of the von Hippel-Lindau protein (pVHL). An emblematic feature of RH is the high vascularity, which is explained by the overexpression of angiogenic factors (AFs) arising from the pVHL impairment. The introduction of Optical Coherence Tomography Angiography (OCTA) allowed observing this feature with exceptional detail. Here, we combine OCTA images and a mechanistic model to investigate tumor growth and vascular development in a patient-specific way. We derived our model from the agreed pathology for RH and focused on the earliest stages of tumor-induced angiogenesis. Our simulations closely resemble the medical images, supporting the capability of our model to simulate vascular patterning in actual patients. Our results also suggest that angiogenesis in RH occurs upon reaching a critical dimension (around 200 μm), followed by the rapid formation of stable vascular networks. These findings open a new perspective on the crucial role of time in antiangiogenic therapy in RH, which has resulted in ineffective control. Indeed, it might be that when RH is diagnosed, angiogenesis is already too advanced to be effectively targeted with any effective means. Moreover, our simulations suggest that vascularization in RH is not a continuous process but an inconstant development with long, stable phases and rapid episodes of vascular sprouting.},

note = {Cited by: 1; Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{SCOPUS_ID:85194767977,

title = {Catechol-induced covalent modifications modulate the aggregation tendency of α-synuclein: An in-solution and in-silico study},

author = {Ilenia Inciardi and Elena Rizzotto and Francesco Gregoris and Benedetta Fongaro and Alice Sosic and Giovanni Minervini and Patrizia Polverino Laureto},

url = {https://www.scopus.com/record/display.uri?eid=2-s2.0-85194767977&origin=inward},

doi = {10.1002/biof.2086},

year  = {2025},

date = {2025-01-01},

journal = {BioFactors},

volume = {51},

number = {1},

publisher = {John Wiley and Sons Inc},

abstract = {© 2024 International Union of Biochemistry and Molecular Biology.Parkinson's disease (PD) stands as a challenging neurodegenerative condition characterized by the emergence of Lewy Bodies (LBs), intracellular inclusions within dopaminergic neurons. These LBs harbor various proteins, prominently including α-Synuclein (Syn) aggregates, implicated in disease pathology. A promising avenue in PD treatment involves targeting Syn aggregation. Recent findings from our research have shown that 3,4-dihydroxyphenylacetic acid (DOPAC) and 3,4-dihydroxyphenylethanol (DOPET) possess the ability to impede the formation of Syn fibrils by disrupting the aggregation process. Notably, these compounds primarily engage in noncovalent interactions with the protein, leading to the formation of off-pathway oligomers that deter fibril growth. Through proteolysis studies and mass spectrometry (MS) analysis, we have identified potential covalent modifications of Syn in the presence of DOPAC, although the exact site remains elusive. Employing molecular dynamics simulations, we delved into how DOPAC-induced covalent alterations might affect the mechanism of Syn aggregation. Our findings indicate that the addition of a covalent adduct on certain residues enhances fibril flexibility without compromising its secondary structure stability. Furthermore, in the monomeric state, the modified residue fosters novel bonding interactions, thereby influencing long-range interactions between the N- and C-termini of the protein.},

note = {Cited by: 3; Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{SCOPUS_ID:105017879475,

title = {Mapping cryptic phosphorylation sites in the human proteome},

author = {Dino Gasparotto and Annarita Zanon and Valerio Bonaldo and Elisa Marchiori and Massimo Casagranda and Erika Di Domenico and Laura Copat and Tommaso Fortunato Asquini and Marta Rigoli and Sirio Vittorio Feltrin and Nuria Lopez Lorenzo and Graziano Lolli and Maria Pennuto and Jesùs R Requena and Omar Rota Stabelli and Giovanni Minervini and Cristian Micheletti and Giovanni Spagnolli and Pietro Faccioli and Emiliano Biasini},

url = {https://www.scopus.com/record/display.uri?eid=2-s2.0-105017879475&origin=inward},

doi = {10.1038/s44318-025-00567-1},

year  = {2025},

date = {2025-01-01},

journal = {EMBO Journal},

volume = {44},

number = {22},

pages = {6704-6731},

publisher = {Springer Science and Business Media Deutschland GmbH},

abstract = {© The Author(s) 2025.Advances in computational and experimental methods have revealed the existence of transient, non-native protein folding intermediates that could play roles in disparate biological processes, from regulation of protein expression to disease-relevant misfolding mechanisms. Here, we tested the possibility that specific post-translational modifications may involve residues exposed during the folding process by assessing the solvent accessibility of 87,138 post-translationally modified amino acids in the human proteome. Unexpectedly, we found that one-third of phosphorylated proteins present at least one phosphosite completely buried within the protein’s inner core. Computational and experimental analyses suggest that these cryptic phosphosites may become exposed during the folding process, where their modification could destabilize native structures and trigger protein degradation. Phylogenetic investigation also reveals that cryptic phosphosites are more conserved than surface-exposed phosphorylated residues. Finally, cross-referencing with cancer mutation databases suggests that phosphomimetic mutations in cryptic phosphosites can increase tumor fitness by inactivating specific onco-suppressors. These findings define a novel role for co-translational phosphorylation in shaping protein folding and expression, laying the groundwork for exploring the implications of cryptic phosphorylation in health and disease.},

note = {Cited by: 1; Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}