Silvio C. E. Tosatto

@article{DelConte2024W306,

title = {RING 4.0: Faster residue interaction networks with novel interaction types across over 35,000 different chemical structures},

author = {Alessio Del Conte and Giorgia F Camagni and Damiano Clementel and Giovanni Minervini and Alexander Miguel Monzon and Carlo Ferrari and Damiano Piovesan and Silvio C. E Tosatto},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85197788039\&doi=10.109%2fna%2fgkae337\&partnerID=40\&md5=bca70d16fbb39f5466a3957673ef9eef},

doi = {10.1093/nar/gkae337},

issn = {03051048},

year  = {2024},

date = {2024-01-01},

journal = {Nucleic Acids Research},

volume = {52},

number = {W1},

pages = {W306 \textendash W312},

publisher = {Oxford University Press},

abstract = {Residue interaction networks (RINs) are a valuable approach for representing contacts in protein structures. RINs have been widely used in various research areas, including the analysis of mutation effects, domain-domain communication, catalytic activity, and molecular dynamics simulations. The RING server is a powerful tool to calculate non-covalent molecular interactions based on geometrical parameters, providing high-quality and reliable results. Here, we introduce RING 4.0, which includes significant enhancements for identifying both covalent and non-covalent bonds in protein structures. It now encompasses seven different interaction types, with the addition of π-hydrogen, halogen bonds and metal ion coordination sites. The definitions of all available bond types have also been refined and RING can now process the complete PDB chemical component dictionary (over 35000 different molecules) which provides atom names and covalent connectivity information for all known ligands. Optimization of the software has improved execution time by an order of magnitude. The RING web server has been redesigned to provide a more engaging and interactive user experience, incorporating new visualization tools. Users can now visualize all types of interactions simultaneously in the structure viewer and network component. The web server, including extensive help and tutorials, is available from URL: https://ring.biocomputingup.it/. © 2024 The Author(s). Published by Oxford University Press on behalf of Nucleic Acids Research.},

note = {Cited by: 5; All Open Access, Gold Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Quaglia2024,

title = {Best practices for the manual curation of intrinsically disordered proteins in DisProt},

author = {Federica Quaglia and Anastasia Chasapi and Maria Victoria Nugnes and Maria Cristina Aspromonte and Emanuela Leonardi and Damiano Piovesan and Silvio C. E. Tosatto},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85188297172\&doi=10.109%2fdatabas%2fbaae009\&partnerID=40\&md5=df4fca19479789139b3fd19bb35c817f},

doi = {10.1093/database/baae009},

issn = {17580463},

year  = {2024},

date = {2024-01-01},

journal = {Database},

volume = {2024},

publisher = {Oxford University Press},

abstract = {The DisProt database is a resource containing manually curated data on experimentally validated intrinsically disordered proteins (IDPs) and intrinsically disordered regions (IDRs) from the literature. Developed in 2005, its primary goal was to collect structural and functional information into proteins that lack a fixed three-dimensional structure.Today, DisProt has evolved into a major repository that not only collects experimental data but also contributes to our understanding of the IDPs/IDRs roles in various biological processes, such as autophagy or the life cycle mechanisms in viruses or their involvement in diseases (such as cancer and neurodevelopmental disorders). DisProt offers detailed information on the structural states of IDPs/IDRs, including state transitions, interactions and their functions, all provided as curated annotations. One of the central activities of DisProt is the meticulous curation of experimental data from the literature. For this reason, to ensure that every expert and volunteer curator possesses the requisite knowledge for data evaluation, collection and integration, training courses and curation materials are available. However, biocuration guidelines concur on the importance of developing robust guidelines that not only provide critical information about data consistency but also ensure data acquisition.This guideline aims to provide both biocurators and external users with best practices for manually curating IDPs and IDRs in DisProt. It describes every step of the literature curation process and provides use cases of IDP curation within DisProt. © The Author(s) 2024. Published by Oxford University Press.},

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

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Arr\'{i}as2024,

title = {Diversity and structural-functional insights of alpha-solenoid proteins},

author = {Paula Nazarena Arr\'{i}as and Zarifa Osmanli and Estefan\'{i}a Peralta and Patricio Manuel Chinestrad and Alexander Miguel Monzon and Silvio C. E. Tosatto},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85207813713\&doi=10.100%2fpro.5189\&partnerID=40\&md5=846b239a4c9a4105e9b257d05a64e1fb},

doi = {10.1002/pro.5189},

issn = {09618368},

year  = {2024},

date = {2024-01-01},

journal = {Protein Science},

volume = {33},

number = {11},

publisher = {John Wiley and Sons Inc},

abstract = {Alpha-solenoids are a significant and diverse subset of structured tandem repeat proteins (STRPs) that are important in various domains of life. This review examines their structural and functional diversity and highlights their role in critical cellular processes such as signaling, apoptosis, and transcriptional regulation. Alpha-solenoids can be classified into three geometric folds: low curvature, high curvature, and corkscrew, as well as eight subfolds: ankyrin repeats; Huntingtin, elongation factor 3, protein phosphatase 2A, and target of rapamycin; armadillo repeats; tetratricopeptide repeats; pentatricopeptide repeats; Pumilio repeats; transcription activator-like; and Sel-1 and Sel-1-like repeats. These subfolds represent distinct protein families with unique structural properties and functions, highlighting the versatility of alpha-solenoids. The review also discusses their association with disease, highlighting their potential as therapeutic targets and their role in protein design. Advances in state-of-the-art structure prediction methods provide new opportunities and challenges in the functional characterization and classification of this kind of fold, emphasizing the need for continued development of methods for their identification and proper data curation and deposition in the main databases. © 2024 The Author(s). Protein Science published by Wiley Periodicals LLC on behalf of The Protein Society.},

note = {Cited by: 0; All Open Access, Hybrid Gold Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Piovesan2024,

title = {CAFA-evaluator: a Python tool for benchmarking ontological classification methods},

author = {Damiano Piovesan and Davide Zago and Parnal Joshi and M. Clara De Paolis Kaluza and Mahta Mehdiabadi and Rashika Ramola and Alexander Miguel Monzon and Walter Reade and Iddo Friedberg and Predrag Radivojac and Silvio C. E. Tosatto},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85188993912\&doi=10.109%2fbioad%2fvbae043\&partnerID=40\&md5=b6e09ea188a60708097f5bc31ba115dd},

doi = {10.1093/bioadv/vbae043},

issn = {26350041},

year  = {2024},

date = {2024-01-01},

journal = {Bioinformatics Advances},

volume = {4},

number = {1},

publisher = {Oxford University Press},

abstract = {We present CAFA-evaluator, a powerful Python program designed to evaluate the performance of prediction methods on targets with hierarchical concept dependencies. It generalizes multi-label evaluation to modern ontologies where the prediction targets are drawn from a directed acyclic graph and achieves high efficiency by leveraging matrix computation and topological sorting. The program requirements include a small number of standard Python libraries, making CAFA-evaluator easy to maintain. The code replicates the Critical Assessment of protein Function Annotation (CAFA) benchmarking, which evaluates predictions of the consistent subgraphs in Gene Ontology. Owing to its reliability and accuracy, the organizers have selected CAFA-evaluator as the official CAFA evaluation software. © 2024 The Author(s). Published by Oxford University Press.},

note = {Cited by: 2; All Open Access, Gold Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Bellanda2024,

title = {A PDZ scaffolding/CaM-mediated pathway in Cryptochrome signaling},

author = {Massimo Bellanda and Milena Damulewicz and Barbara Zambelli and Elisa Costanzi and Francesco Gregoris and Stefano Mammi and Silvio C. E. Tosatto and Rodolfo Costa and Giovanni Minervini and Gabriella M. Mazzotta},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85185346556\&doi=10.100%2fpro.4914\&partnerID=40\&md5=9d3ca7169c5c85e7e43289adbe2c3e24},

doi = {10.1002/pro.4914},

issn = {09618368},

year  = {2024},

date = {2024-01-01},

journal = {Protein Science},

volume = {33},

number = {3},

publisher = {John Wiley and Sons Inc},

abstract = {Cryptochromes are cardinal constituents of the circadian clock, which orchestrates daily physiological rhythms in living organisms. A growing body of evidence points to their participation in pathways that have not traditionally been associated with circadian clock regulation, implying that cryptochromes may be subject to modulation by multiple signaling mechanisms. In this study, we demonstrate that human CRY2 (hCRY2) forms a complex with the large, modular scaffolding protein known as Multi-PDZ Domain Protein 1 (MUPP1). This interaction is facilitated by the calcium-binding protein Calmodulin (CaM) in a calcium-dependent manner. Our findings suggest a novel cooperative mechanism for the regulation of mammalian cryptochromes, mediated by calcium ions (Ca2+) and CaM. We propose that this Ca2+/CaM-mediated signaling pathway may be an evolutionarily conserved mechanism that has been maintained from Drosophila to mammals, most likely in relation to its potential role in the broader context of cryptochrome function and regulation. Further, the understanding of cryptochrome interactions with other proteins and signaling pathways could lead to a better definition of its role within the intricate network of molecular interactions that govern circadian rhythms. © 2024 The Protein Society.},

note = {Cited by: 0},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Gregoris2024,

title = {In Silico Exploration of AHR-HIF Pathway Interplay: Implications for Therapeutic Targeting in ccRCC},

author = {Francesco Gregoris and Giovanni Minervini and Silvio C. E. Tosatto},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85205114282\&doi=10.339%2fgenes15091167\&partnerID=40\&md5=4358b236c257d898f6c44e2639ebbd9d},

doi = {10.3390/genes15091167},

issn = {20734425},

year  = {2024},

date = {2024-01-01},

journal = {Genes},

volume = {15},

number = {9},

publisher = {Multidisciplinary Digital Publishing Institute (MDPI)},

abstract = {The oxygen-sensing pathway is a crucial regulatory circuit that defines cellular conditions and is extensively exploited in cancer development. Pathogenic mutations in the von Hippel\textendashLindau (VHL) tumour suppressor impair its role as a master regulator of hypoxia-inducible factors (HIFs), leading to constitutive HIF activation and uncontrolled angiogenesis, increasing the risk of developing clear cell renal cell carcinoma (ccRCC). HIF hyperactivation can sequester HIF-1β, preventing the aryl hydrocarbon receptor (AHR) from correctly activating gene expression in response to endogenous and exogenous ligands such as TCDD (dioxins). In this study, we used protein\textendashprotein interaction networks and gene expression profiling to characterize the impact of VHL loss on AHR activity. Our findings reveal specific expression patterns of AHR interactors following exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and in ccRCC. We identified several AHR interactors significantly associated with poor survival rates in ccRCC patients. Notably, the upregulation of the androgen receptor (AR) and retinoblastoma-associated protein (RB1) by TCDD, coupled with their respective downregulation in ccRCC and association with poor survival rates, suggests novel therapeutic targets. The strategic activation of the AHR via selective AHR modulators (SAhRMs) could stimulate its anticancer activity, specifically targeting RB1 and AR to reduce cell cycle progression and metastasis formation in ccRCC. Our study provides comprehensive insights into the complex interplay between the AHR and HIF pathways in ccRCC pathogenesis, offering novel strategies for targeted therapeutic interventions. © 2024 by the authors.},

note = {Cited by: 0; All Open Access, Gold Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Aspromonte2024D434,

title = {DisProt in 2024: improving function annotation of intrinsically disordered proteins},

author = {Maria Cristina Aspromonte and Maria Victoria Nugnes and Federica Quaglia and Adel Bouharoua and Silvio C. E. Tosatto and Damiano Piovesan and Vasileios Sagris and Vasilis J. Promponas and Anastasia Chasapi and Erzs\'{e}bet Fich\'{o} and Galo E. Balatti and Gustavo Parisi and Mart\'{i}n Gonz\'{a}lez Buitr\'{o}n and Gabor Erdos and Matyas Pajkos and Zsuzsanna Doszt\'{a}nyi and Laszlo Dobson and Alessio Del Conte and Damiano Clementel and Edoardo Salladini and Emanuela Leonardi and Fatemeh Kordevani and Hamidreza Ghafouri and Luiggi G. Tenorio Ku and Alexander Miguel Monzon and Carlo Ferrari and Zs\'{o}fia K\'{a}lm\'{a}n and Juliet F. Nilsson and Jaime Santos and Carlos Pintado-Grima and Salvador Ventura and Veronika \'{A}cs and Rita Pancsa and Mariane Goncalves Kulik and Miguel A. Andrade-Navarro and Pedro Jos\'{e} Barbosa Pereira and Sonia Longhi and Philippe Le Mercier and Julian Bergier and Peter Tompa and Tamas Lazar},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85176208048\&doi=10.109%2fna%2fgkad928\&partnerID=40\&md5=fc34ce08667ff42029fdb54d5142c08f},

doi = {10.1093/nar/gkad928},

issn = {03051048},

year  = {2024},

date = {2024-01-01},

journal = {Nucleic Acids Research},

volume = {52},

number = {D1},

pages = {D434 \textendash D441},

publisher = {Oxford University Press},

abstract = {DisProt (URL: https://disprot.org) is the gold standard database for intrinsically disordered proteins and regions, providing valuable information about their functions. The latest version of DisProt brings significant advancements, including a broader representation of functions and an enhanced curation process. These improvements aim to increase both the quality of annotations and their coverage at the sequence level. Higher coverage has been achieved by adopting additional evidence codes. Quality of annotations has been improved by systematically applying Minimum Information About Disorder Experiments (MIADE) principles and reporting all the details of the experimental setup that could potentially influence the structural state of a protein. The DisProt database now includes new thematic datasets and has expanded the adoption of Gene Ontology terms, resulting in an extensive functional repertoire which is automatically propagated to UniProtKB. Finally, we show that DisProt’s curated annotations strongly correlate with disorder predictions inferred from AlphaFold2 pLDDT (predicted Local Distance Difference Test) confidence scores. This comparison highlights the utility of DisProt in explaining apparent uncertainty of certain well-defined predicted structures, which often correspond to folding-upon-binding fragments. Overall, DisProt serves as a comprehensive resource, combining experimental evidence of disorder information to enhance our understanding of intrinsically disordered proteins and their functional implications. © The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.},

note = {Cited by: 15; All Open Access, Gold Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Ghafouri2024D536,

title = {PED in 2024: improving the community deposition of structural ensembles for intrinsically disordered proteins},

author = {Hamidreza Ghafouri and Tamas Lazar and Alessio Del Conte and Luiggi G. Tenorio Ku and Peter Tompa and Silvio C. E. Tosatto and Alexander Miguel Monzon and Maria C. Aspromonte and Pau Bernad\'{o} and Bel\'{e}n Chaves-Arquero and Lucia Beatriz Chemes and Damiano Clementel and Tiago N. Cordeiro and Carlos A. Elena-Real and Michael Feig and Isabella C. Felli and Carlo Ferrari and Julie D. Forman-Kay and Tiago Gomes and Frank Gondelaud and Claudiu C. Gradinaru and T\^{a}p Ha-Duong and Teresa Head-Gordon and P\'{e}tur O. Heidarsson and Giacomo Janson and Gunnar Jeschke and Emanuela Leonardi and Zi Hao Liu and Sonia Longhi and Xamuel L. Lund and Maria J. Macias and Pau Martin-Malpartida and Davide Mercadante and Assia Mouhand and Gabor Nagy and Mar\'{i}a Victoria Nugnes and Jos\'{e} Manuel P\'{e}rez-Ca\~{n}adillas and Giulia Pesce and Roberta Pierattelli and Damiano Piovesan and Federica Quaglia and Sylvie Ricard-Blum and Paul Robustelli and Amin Sagar and Edoardo Salladini and Lucile S\'{e}nicourt and Nathalie Sibille and Jo\~{a}o M. C. Teixeira and Thomas E. Tsangaris and Mihaly Varadi},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85181761325\&doi=10.109%2fna%2fgkad947\&partnerID=40\&md5=0ad51562357f3e5f603d744e02f8729a},

doi = {10.1093/nar/gkad947},

issn = {03051048},

year  = {2024},

date = {2024-01-01},

journal = {Nucleic Acids Research},

volume = {52},

number = {D1},

pages = {D536 \textendash D544},

publisher = {Oxford University Press},

abstract = {The Protein Ensemble Database (PED) (URL: https://proteinensemble.org) is the primary resource for depositing structural ensembles of intrinsically disordered proteins. This updated version of PED reflects advancements in the field, denoting a continual expansion with a total of 461 entries and 538 ensembles, including those generated without explicit experimental data through novel machine learning (ML) techniques. With this significant increment in the number of ensembles, a few yet-unprecedented new entries entered the database, including those also determined or refined by electron paramagnetic resonance or circular dichroism data. In addition, PED was enriched with several new features, including a novel deposition service, improved user interface, new database cross-referencing options and integration with the 3D-Beacons network\textemdashall representing efforts to improve the FAIRness of the database. Foreseeably, PED will keep growing in size and expanding with new types of ensembles generated by accurate and fast ML-based generative models and coarse-grained simulations. Therefore, among future efforts, priority will be given to further develop the database to be compatible with ensembles modeled at a coarse-grained level. © The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.},

note = {Cited by: 13; All Open Access, Gold Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Piol2023,

title = {Antagonistic effect of cyclin-dependent kinases and a calcium-dependent phosphatase on polyglutamine-expanded androgen receptor toxic gain of function},

author = {Diana Piol and Laura Tosatto and Emanuela Zuccaro and Eric N. Anderson and Antonella Falconieri and Maria J. Polanco and Caterina Marchioretti and Federica Lia and Joseph White and Elisa Bregolin and Giovanni Minervini and Sara Parodi and Xavier Salvatella and Giorgio Arrigoni and Andrea Ballabio and Albert R. La Spada and Silvio C. E. Tosatto and Fabio Sambataro and Diego L. Medina and Udai B. Pandey and Manuela Basso and Maria Pennuto},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85145870213\&doi=10.112%2fsciadv.ade1694\&partnerID=40\&md5=47b819a09fd41c1bb6bde30c1401e4f7},

doi = {10.1126/sciadv.ade1694},

issn = {23752548},

year  = {2023},

date = {2023-01-01},

journal = {Science Advances},

volume = {9},

number = {1},

publisher = {American Association for the Advancement of Science},

abstract = {Spinal and bulbar muscular atrophy is caused by polyglutamine (polyQ) expansions in androgen receptor (AR), generating gain-of-function toxicity that may involve phosphorylation. Using cellular and animal models, we investigated what kinases and phosphatases target polyQ-expanded AR, whether polyQ expansions modify AR phosphorylation, and how this contributes to neurodegeneration. Mass spectrometry showed that polyQ expansions preserve native phosphorylation and increase phosphorylation at conserved sites controlling AR stability and transactivation. In small-molecule screening, we identified that CDC25/CDK2 signaling could enhance AR phosphorylation, and the calcium-sensitive phosphatase calcineurin had opposite effects. Pharmacologic and genetic manipulation of these kinases and phosphatases modified polyQ-expanded AR function and toxicity in cells, flies, and mice. Ablation of CDK2 reduced AR phosphorylation in the brainstem and restored expression of Myc and other genes involved in DNA damage, senescence, and apoptosis, indicating that the cell cycle\textendashregulated kinase plays more than a bystander role in SBMA-vulnerable postmitotic cells. Copyright © 2023 The Authors, some rights reserved;},

note = {Cited by: 6; All Open Access, Gold Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Conte20231925,

title = {Critical assessment of protein intrinsic disorder prediction (CAID) - Results of round 2},

author = {Alessio Del Conte and Mahta Mehdiabadi and Adel Bouhraoua and Alexander Miguel Monzon and Silvio C. E. Tosatto and Damiano Piovesan},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85169117009\&doi=10.100%2fprot.26582\&partnerID=40\&md5=20d7d0ec6f796c0901f2a365becf7fa6},

doi = {10.1002/prot.26582},

issn = {08873585},

year  = {2023},

date = {2023-01-01},

journal = {Proteins: Structure, Function and Bioinformatics},

volume = {91},

number = {12},

pages = {1925 \textendash 1934},

publisher = {John Wiley and Sons Inc},

abstract = {Protein intrinsic disorder (ID) is a complex and context-dependent phenomenon that covers a continuum between fully disordered states and folded states with long dynamic regions. The lack of a ground truth that fits all ID flavors and the potential for order-to-disorder transitions depending on specific conditions makes ID prediction challenging. The CAID2 challenge aimed to evaluate the performance of different prediction methods across different benchmarks, leveraging the annotation provided by the DisProt database, which stores the coordinates of ID regions when there is experimental evidence in the literature. The CAID2 challenge demonstrated varying performance of different prediction methods across different benchmarks, highlighting the need for continued development of more versatile and efficient prediction software. Depending on the application, researchers may need to balance performance with execution time when selecting a predictor. Methods based on AlphaFold2 seem to be good ID predictors but they are better at detecting absence of order rather than ID regions as defined in DisProt. The CAID2 predictors can be freely used through the CAID Prediction Portal, and CAID has been integrated into OpenEBench, which will become the official platform for running future CAID challenges. © 2023 The Authors. Proteins: Structure, Function, and Bioinformatics published by Wiley Periodicals LLC.},

note = {Cited by: 20; All Open Access, Hybrid Gold Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}