Article
Biochemistry & Molecular Biology
Seher Abbas, Valerio Marino, Nicole Weisschuh, Sinja Kieninger, Maria Solaki, Daniele Dell'Orco, Karl-Wilhelm Koch
ACS CHEMICAL NEUROSCIENCE
(2020)
Article
Biochemistry & Molecular Biology
Valerio Marino, Matteo Riva, Davide Zamboni, Karl-Wilhelm Koch, Daniele Dell'Orco
Summary: This study investigates the mechanism by which the calcium-sensor protein recoverin regulates the activity of rhodopsin kinase in photoreceptors. The presence of both GRK1 and membrane is crucial for the physiological response to changes in intracellular calcium levels, driving the structural transitions of recoverin via a conformational selection mechanism. These findings may have implications for other sensory transduction systems involving protein complexes and biological membranes.
Editorial Material
Biochemistry & Molecular Biology
Daniele Dell'Orco
Summary: The study investigated the interaction between calmodulin and peptides mimicking different structural regions of the cardiac ryanodine receptor at varying calcium concentrations. It identified the specific CaM domains that bind to the CaM-binding domain in RyR2, showing that the interaction occurs under Ca2+-saturating conditions. This methodology may have broad applicability to the study of Ca2+ signaling and diseases associated with mutations in CaM-encoding genes.
BIOCHEMICAL JOURNAL
(2021)
Article
Biochemistry & Molecular Biology
Ulrich Kellner, Nicole Weisschuh, Silke Weinitz, Ghazaleh Farmand, Sebastian Deutsch, Friederike Kortum, Pascale Mazzola, Karin Schaferhoff, Valerio Marino, Daniele Dell'Orco
Summary: A novel missense variant in the C1QTNF5 gene (p.(Q180E)) was found to cause autosomal dominant gyrate atrophy-like choroidal dystrophy (adGALCD) with unique clinical features compared to late-onset retinal degeneration (LORD). Protein tertiary and quaternary structure destabilization due to the variant was proposed as the mechanism behind the specific phenotype observed.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Valerio Marino, Giuditta Dal Cortivo, Paolo Enrico Maltese, Giorgio Placidi, Elisa De Siena, Benedetto Falsini, Matteo Bertelli, Daniele Dell'Orco
Summary: This study presents a novel GCAP1 variant associated with cone dystrophy (COD), characterized by severe alterations in electroretinogram under both scotopic and photopic conditions. Biochemical and biophysical analysis revealed compromised Ca2+-sensitivity of the variant, leading to constitutive activation of guanylate cyclase at physiological Ca2+ levels. The dysregulation of the GCAP1-cyclase complex not only affects second messenger accumulation and cell death, but also disrupts synaptic communication with bipolar cells, ultimately altering the ON-pathway related to b-wave generation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Giuditta Dal Cortivo, Carlo Giorgio Barracchia, Valerio Marino, Mariapina D'Onofrio, Daniele Dell'Orco
Summary: Mutations associated with lethal arrhythmia in Calmodulin alter protein-protein interaction with Ryanodine receptor 2. Mutants show common alterations in recognition and faster dissociation rate than wild-type CaM. CaM's N-terminal lobe interacts with the target through allosteric interactions initiated by Ca2+.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Nicole Weisschuh, Valerio Marino, Karin Schaeferhoff, Paul Richter, Joohyun Park, Tobias B. Haack, Daniele Dell'Orco
Summary: Exonic variants in disease-associated genes can have pathogenic effects by altering amino acid sequences or affecting pre-mRNA splicing. This study focused on analyzing nine exonic nucleotide changes in the GTPase-encoding domain of OPA1, a major gene underlying dominant optic atrophy. Different outcomes were observed for variants at codon 438, with some destabilizing dimerization and others causing exon skipping. The combination of RNA analysis and protein modeling proved valuable in assigning patients to precision therapies.
HUMAN MOLECULAR GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Amedeo Biasi, Valerio Marino, Giuditta Dal Cortivo, Paolo Enrico Maltese, Antonio Mattia Modarelli, Matteo Bertelli, Leonardo Colombo, Daniele Dell'Orco
Summary: This study identified a novel variant of GUCA1A causing an amino acid substitution in GCAP1, leading to increased affinity with GC and a doubled IC50 value, potentially resulting in hyper-activity of GC and toxic accumulation of cGMP and Ca2+, ultimately triggering cell death in photoreceptor cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Genetics & Heredity
Paola Tesolin, Sofia Fiorino, Stefania Lenarduzzi, Elisa Rubinato, Elisabetta Cattaruzzi, Lydie Ammar, Veronica Castro, Eva Orzan, Claudio Granata, Daniele Dell'Orco, Anna Morgan, Giorgia Girotto
Summary: Pendred syndrome is characterized by sensorineural hearing loss, inner ear malformations, and goiter, primarily caused by mutations in the SLC26A4 gene. This study differentiated patient types through deep evaluation, with five patients carrying SLC26A4 variants showing characteristic audiograms and five others carrying different variants. In one patient negative for the SLC26A4 gene, a variant in the MYO5C gene was identified as a potential new candidate gene for hearing loss.
Article
Ophthalmology
Rosa Longo, Anna Avesani, Giulia Dalla Mura, Daniele Dell'Orco, Stefano Manfredini, Giacomo Panozzo
Summary: Treatment with U-HACL tear substitute resulted in significant improvement of ocular surface status in dry eye patients, as evidenced by improvements in symptoms, tear film parameters, and corneal/conjunctival damage scores.
EXPERT REVIEW OF OPHTHALMOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Giuditta Dal Cortivo, Daniele Dell'Orco
Summary: CIB2 is a protein capable of binding calcium and magnesium ions, playing an important role in cochlear hair cells and being associated with non-syndromic deafness. Besides its involvement in auditory physiology, CIB2 has diverse functions in various processes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Anna Avesani, Laura Bielefeld, Nicole Weisschuh, Valerio Marino, Pascale Mazzola, Katarina Stingl, Tobias B. Haack, Karl-Wilhelm Koch, Daniele Dell'Orco
Summary: This study characterizes the biochemical and biophysical properties of human GCAP3 and identifies a mutation in GUCA1C that may contribute to retinitis pigmentosa.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Jan-Philipp Bodenbender, Valerio Marino, Leon Bethge, Katarina Stingl, Tobias B. B. Haack, Saskia Biskup, Susanne Kohl, Laura Kuehlewein, Daniele Dell'Orco, Nicole Weisschuh
Summary: This study analyzed clinical heterogeneity and characterized the underlying biallelic variants in TULP1 in 17 patients. The majority of patients exhibited severe rod-driven inherited retinal degeneration, while a fraction of the patients had cone-driven disease. The findings support the hypothesis that TULP1 variants lead to misfolding and trigger unfolded protein response, resulting in photoreceptor death.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Sabrina Asteriti, Valerio Marino, Anna Avesani, Amedeo Biasi, Giuditta Dal Cortivo, Lorenzo Cangiano, Daniele Dell'Orco
Summary: This study explored the possibility of modulating the phototransduction cascade in mouse rods using direct or liposome-mediated administration of a recombinant protein. The results showed that the exogenous protein was fully incorporated into the mouse retina and induced a disease-like electrophysiological phenotype in the presence of a specific mutation. These findings are important for the treatment of autosomal dominant genetic diseases.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Anna Avesani, Valerio Marino, Serena Zanzoni, Karl-Wilhelm Koch, Daniele Dell'Orco
Summary: Human GCAP2 and its G157R variant exhibit differences in biochemical properties and may be associated with inherited retinal degeneration.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)