Ermanna Rovida
Ricercatore ( Researcher)
Area of interest:
Molecular modeling, protein docking and molecular dynamics simulation for the prediction of protein structure, mutant analysis and design, ligand binding and protein-protein interaction. Computational analysis of naturally occurring mutants and polymorphisms of proteins implicated in different pathological conditions including coagulation and iron metabolism disorders.
Most significant publications:
2015
Levi, Sonia; Rovida, Ermanna
Neuroferritinopathy: From ferritin structure modification to pathogenetic mechanism Journal Article
In: Neurobiology of Disease, 81 , pp. 134–143, 2015, ISSN: 1095-953X.
@article{levi_neuroferritinopathy:_2015,
title = {Neuroferritinopathy: From ferritin structure modification to pathogenetic mechanism},
author = {Sonia Levi and Ermanna Rovida},
doi = {10.1016/j.nbd.2015.02.007},
issn = {1095-953X},
year = {2015},
date = {2015-09-01},
journal = {Neurobiology of Disease},
volume = {81},
pages = {134--143},
abstract = {Neuroferritinopathy is a rare, late-onset, dominantly inherited movement disorder caused by mutations in L-ferritin gene. It is characterized by iron and ferritin aggregate accumulation in brain, normal or low serum ferritin levels and high variable clinical feature. To date, nine causative mutations have been identified and eight of them are frameshift mutations determined by nucleotide(s) insertion in the exon 4 of L-ferritin gene altering the structural conformation of the C-terminus of the L-ferritin subunit. Acting in a dominant negative manner, mutations are responsible for an impairment of the iron storage efficiency of ferritin molecule. Here, we review the main characteristics of neuroferritinopathy and present a computational analysis of some representative recently defined mutations with the purpose to gain new information about the pathogenetic mechanism of the disorder. This is particularly important as neuroferritinopathy can be considered an interesting model to study the relationship between iron, oxidative stress and neurodegeneration.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
D'Ursi, Pasqualina; Orro, Alessandro; Morra, Giulia; Moscatelli, Marco; Trombetti, Gabriele; Milanesi, Luciano; Rovida, Ermanna
In: Journal of Biomolecular Structure & Dynamics, 33 (1), pp. 85–92, 2015, ISSN: 1538-0254.
@article{dursi_molecular_2015,
title = {Molecular dynamics and docking simulation of a natural variant of Activated Protein C with impaired protease activity: implications for integrin-mediated antiseptic function},
author = {Pasqualina D'Ursi and Alessandro Orro and Giulia Morra and Marco Moscatelli and Gabriele Trombetti and Luciano Milanesi and Ermanna Rovida},
doi = {10.1080/07391102.2013.851033},
issn = {1538-0254},
year = {2015},
date = {2015-01-01},
journal = {Journal of Biomolecular Structure & Dynamics},
volume = {33},
number = {1},
pages = {85--92},
abstract = {Activated Protein C (APC) is a multifunctional serine protease, primarily known for its anticoagulant function in the coagulation system. Several studies have already elucidated its role in counteracting apoptosis and inflammation in cells, while significant effort is still ongoing for defining its involvement in sepsis. Earlier literature has shown that the antiseptic function of APC is mediated by its binding to leukocyte integrins, which is due to the presence of the integrin binding motif Arg-Gly-Asp at the N-terminus of the APC catalytic chain. Many natural mutants have been identified in patients with Protein C deficiency diagnosis including a variant of specificity pocket (Gly216Asp). In this work, we present a molecular model of the complex of APC with αVβ3 integrin obtained by protein-protein docking approach. A computational analysis of this variant is hereby presented, based on molecular dynamics and docking simulations, aiming at investigating the effects of the Gly216Asp mutation on the protein conformation and inferring its functional implications. Our study shows that such mutation is likely to impair the protease activity while preserving the overall protein fold. Moreover, superposition of the integrin binding motifs in wild-type and mutant forms suggests that the interaction with integrin can still occur and thus the mutant is likely to retain its antiseptic function related to the neutrophyl integrin binding. Therapeutic applications could result in this APC mutant which retains antiseptic function without anticoagulant side effects.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
2014
Biunno, Ida; Aceto, Gitana; Awadelkarim, Khalid Dafaallah; Morgano, Annalisa; Elhaj, Ahmed; Eltayeb, Elgaylani Abdalla; Abuidris, Dafalla Omer; Elwali, Nasr Eldin; Spinelli, Chiara; Blasio, Pasquale De; Rovida, Ermanna; Mariani-Costantini, Renato
BRCA1 point mutations in premenopausal breast cancer patients from Central Sudan Journal Article
In: Familial Cancer, 13 (3), pp. 437–444, 2014, ISSN: 1573-7292.
@article{biunno_brca1_2014,
title = {BRCA1 point mutations in premenopausal breast cancer patients from Central Sudan},
author = {Ida Biunno and Gitana Aceto and Khalid Dafaallah Awadelkarim and Annalisa Morgano and Ahmed Elhaj and Elgaylani Abdalla Eltayeb and Dafalla Omer Abuidris and Nasr Eldin Elwali and Chiara Spinelli and Pasquale {De Blasio} and Ermanna Rovida and Renato Mariani-Costantini},
doi = {10.1007/s10689-014-9717-4},
issn = {1573-7292},
year = {2014},
date = {2014-09-01},
journal = {Familial Cancer},
volume = {13},
number = {3},
pages = {437--444},
abstract = {Premenopausal breast cancer (BC) is one of the most common cancers of women in rural Africa and part of the disease load may be related to hereditary predisposition, including mutations in the BRCA1 gene. However, the BRCA1 mutations associated with BC in Africa are scarcely characterized. We report here 33 BRCA1 point mutations, among which 2 novel missense variants, found in 59 Central Sudanese premenopausal BC patients. The high fractions of mutations with intercontinental and uniquely African distribution (17/33, 51.5 % and 14/33, 42.4 %, respectively) are in agreement with the high genetic diversity expected in an African population. Overall 24/33 variants (72.7 %) resulted neutral; 8/33 of unknown significance (24.3 %, including the 2 novel missense mutations); 1 (3.0 %) overtly deleterious. Notably, in silico studies predict that the novel C-terminal missense variant c.5090G>A (p.Cys1697Tyr) affects phosphopeptide recognition by the BRCA1 BRCT1 domain and may have a pathogenic impact. Genetic variation and frequency of unique or rare mutations of uncertain clinical relevance pose significant challenges to BRCA1 testing in Sudan, as it might happen in other low-resource rural African contexts.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
2012
Cattaneo, Monica; Dominici, Roberto; Cardano, Marina; Diaferia, Giuseppe; Rovida, Ermanna; Biunno, Ida
Molecular chaperones as therapeutic targets to counteract proteostasis defects Journal Article
In: Journal of Cellular Physiology, 227 (3), pp. 1226–1234, 2012, ISSN: 1097-4652.
@article{cattaneo_molecular_2012,
title = {Molecular chaperones as therapeutic targets to counteract proteostasis defects},
author = {Monica Cattaneo and Roberto Dominici and Marina Cardano and Giuseppe Diaferia and Ermanna Rovida and Ida Biunno},
doi = {10.1002/jcp.22856},
issn = {1097-4652},
year = {2012},
date = {2012-03-01},
journal = {Journal of Cellular Physiology},
volume = {227},
number = {3},
pages = {1226--1234},
abstract = {The health of cells is preserved by the levels and correct folding states of the proteome, which is generated and maintained by the proteostasis network, an integrated biological system consisting of several cytoprotective and degradative pathways. Indeed, the health conditions of the proteostasis network is a fundamental prerequisite to life as the inability to cope with the mismanagement of protein folding arising from genetic, epigenetic, and micro-environment stress appears to trigger a whole spectrum of unrelated diseases. Here we describe the potential functional role of the proteostasis network in tumor biology and in conformational diseases debating on how the signaling branches of this biological system may be manipulated to develop more efficacious and selective therapeutic strategies. We discuss the dual strategy of these processes in modulating the folding activity of molecular chaperones in order to counteract the antithetic proteostasis deficiencies occurring in cancer and loss/gain of function diseases. Finally, we provide perspectives on how to improve the outcome of these disorders by taking advantage of proteostasis modeling.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Stenirri, Stefania; Santambrogio, Paolo; Setaccioli, Marco; Erba, Benedetta Gaia; Manitto, Maria Pia; Rovida, Ermanna; Ferrari, Maurizio; Levi, Sonia; Cremonesi, Laura
Study of FTMT and ABCA4 genes in a patient affected by age-related macular degeneration: identification and analysis of new mutations Journal Article
In: Clinical Chemistry and Laboratory Medicine, 50 (6), pp. 1021–1029, 2012, ISSN: 1437-4331.
@article{stenirri_study_2012,
title = {Study of FTMT and ABCA4 genes in a patient affected by age-related macular degeneration: identification and analysis of new mutations},
author = {Stefania Stenirri and Paolo Santambrogio and Marco Setaccioli and Benedetta Gaia Erba and Maria {Pia Manitto} and Ermanna Rovida and Maurizio Ferrari and Sonia Levi and Laura Cremonesi},
doi = {10.1515/cclm-2011-0854},
issn = {1437-4331},
year = {2012},
date = {2012-01-01},
journal = {Clinical Chemistry and Laboratory Medicine},
volume = {50},
number = {6},
pages = {1021--1029},
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a multifactorial disease for which an involvement of alterations in the retinal ABC transporter gene (ABCA4) is still debated. Oxidative stress in retinal pigment epithelial cells has been postulated to contribute to the pathogenesis of the disease. Mitochondrial ferritin (FtMt), an iron-sequestering protein, is expressed in cell types characterized by high metabolic activity and oxygen consumption, including human retina, suggesting a role in protecting mitochondria from iron-dependent oxidative damage. Based on these findings we wanted to investigate whether mutations in this gene could be found in AMD patients.
METHODS: Mutational scanning of the FTMTgene was performed in a cohort of 50 patients affected by age-related macular degeneration. The ABCA4 gene was also scanned in one patient carrying an FtMt mutation. In silico analyses were carried out on the identified variants. The recombinant form of FtMt variant was expressed in Escherichia coli and biochemically characterized.
RESULTS: One patient was found to be heterozygous for two previously unreported genetic changes: a complex FtMt mutation (c.437_450delinsCT: delAGGACATCAAGAAGinsCT) and a missense p.Leu973Phe (c.2919G>T) mutation in exon 20 of ABCA4. Computational analyses predicted a severe structural impairment for FtMt variant and a mild destabilizing effect for ABCA4. E. coli expression of recombinant FtMt variant yielded a highly insoluble protein that could not be renatured under in vitro conditions suitable for wild-type ferritins.
CONCLUSIONS: Our findings suggest that the FtMt mutation may determine a condition similar to haploinsufficiency resulting in a reduced protection from iron-dependent oxidative stress in mitochondria.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
METHODS: Mutational scanning of the FTMTgene was performed in a cohort of 50 patients affected by age-related macular degeneration. The ABCA4 gene was also scanned in one patient carrying an FtMt mutation. In silico analyses were carried out on the identified variants. The recombinant form of FtMt variant was expressed in Escherichia coli and biochemically characterized.
RESULTS: One patient was found to be heterozygous for two previously unreported genetic changes: a complex FtMt mutation (c.437_450delinsCT: delAGGACATCAAGAAGinsCT) and a missense p.Leu973Phe (c.2919G>T) mutation in exon 20 of ABCA4. Computational analyses predicted a severe structural impairment for FtMt variant and a mild destabilizing effect for ABCA4. E. coli expression of recombinant FtMt variant yielded a highly insoluble protein that could not be renatured under in vitro conditions suitable for wild-type ferritins.
CONCLUSIONS: Our findings suggest that the FtMt mutation may determine a condition similar to haploinsufficiency resulting in a reduced protection from iron-dependent oxidative stress in mitochondria.
- Milano
- ermanna.rovida@irgb.cnr.it
- 338 7344267