Andrea Brancaccio

Andrea Brancaccio
Italian National Research Council | CNR · Istituto di Scienze e Tecnologie Chimiche "Giulio Natta" - SCITEC (CNR)

PhD in Biochemistry

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138
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Introduction
He obtained a PhD in Biochemistry at the Sapienza University in Rome, characterizing recombinant myoglobins. In 1994 moved to the Biozentrum in Basel, where he was the main contributor to the elucidation of the very first structural details on α-dystroglycan. In 1998, he moved back to Italy to join CNR where he pursued further work on the dystroglycan subunits and domains as well as on dystroglycan evolution. He is also investigating the role of the agrin-dystroglycan axis in cardiac muscle.

Publications

Publications (138)
Article
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Background Mature cardiomyocytes are unable to proliferate, preventing the injured adult heart from repairing itself. Studies in rodents have suggested that the extracellular matrix protein agrin promotes cardiomyocyte proliferation in the developing heart and that agrin expression is downregulated shortly after birth, resulting in the cessation of...
Article
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The dystroglycan (DG) complex plays a pivotal role for the stabilization of muscles in Metazoa. It is formed by two subunits, extracellular α-DG and transmembrane β-DG, originating from a unique precursor via a complex post-translational maturation process. The α-DG subunit is extensively glycosylated in sequential steps by several specific enzymes...
Article
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[This corrects the article on p. 594 in vol. 8, PMID: 32612983.].
Article
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β-dystroglycan (β-DG) assembles with lamins A/C and B1 and emerin at the nuclear envelope (NE) to maintain proper nuclear architecture and function. To provide insight into the nuclear function of β-DG, we characterized the interaction between β-DG and emerin at the molecular level. Emerin is a major NE protein that regulates multiple nuclear proce...
Article
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Nuclear β-dystroglycan (β-DG) is involved in the maintenance of nuclear architecture and function. Nonetheless, its relevance in defined nuclear processes remains to be determined. In this study we generated a C2C12 cell-based DG-null model using CRISPR-Cas9 technology to provide insights into the role of β-DG on nuclear processes. Since DG-null ce...
Article
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After cardiac injury, the mammalian adult heart has a very limited capacity to regenerate, due to the inability of fully differentiated cardiomyocytes (CMs) to efficiently proliferate. This has been directly linked to the extracellular matrix (ECM) surrounding and connecting cardiomyocytes, as its increasing rigidity during heart maturation has a c...
Article
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The acetylglucosaminyltransferase-like protein LARGE1 is an enzyme that is responsible for the final steps of the post-translational modifications of dystroglycan (DG), a membrane receptor that links the cytoskeleton with the extracellular matrix in skeletal muscle and in a variety of other tissues. LARGE1 acts by adding the repeating disaccharide...
Article
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Dystroglycan (DG) is an adhesion complex that links the cytoskeleton to the surrounding extracellular matrix in skeletal muscle and a wide variety of other tissues. It is composed of a highly glycosylated extracellular α-DG associated noncovalently with a transmembrane β-DG whose cytodomain interacts with dystrophin and its isoforms. Alpha-dystrogl...
Article
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Dystroglycan is a major non‐integrin adhesion complex that connects the cytoskeleton to the surrounding basement membranes, thus providing stability to skeletal muscle. In Vertebrates, hypoglycosylation of α‐dystroglycan has been strongly linked to muscular dystrophy phenotypes, some of which also show variable degrees of cognitive impairments, col...
Article
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Class II chaperonins are essential multisubunit complexes that aid the folding of nonnative proteins in the cytosol of archaea and eukarya. They use energy derived from ATP to drive a series of structural rearrangements that enable polypeptides to fold within their central cavity. These events are regulated by an elaborate allosteric mechanism in n...
Article
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Dystroglycan (DG) is a membrane receptor, belonging to the dystrophin-glycoprotein complex (DGC) and formed by two subunits, α-dystroglycan (α-DG) and β-dystroglycan (β -DG). The C-terminal domain of α-DG and the N-terminal extracellular domain of β -DG are connected, providing a link between the extracellular matrix and the cytosol. Under patholog...
Article
Dystroglycan (DG) is a cell adhesion complex composed by two subunits, the highly glycosylated α-DG and the transmembrane β-DG. In skeletal muscle, DG is involved in dystroglycanopathies, a group of heterogeneous muscular dystrophies characterized by a reduced glycosylation of α-DG. The genes mutated in secondary dystroglycanopathies are involved i...
Cover Page
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On the cover: This cover image, by Giulia Signorino et al., is based on the Research Article A dystroglycan mutation (p.Cys667Phe) associated to muscle-eye-brain disease with multicystic leucodystrophy results in ER-retention of the mutant protein, Pages 266–280. DOI: 10.1002/humu.23370.
Article
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Objective Dystroglycan (DG) is an adhesion complex formed by two subunits, α-DG and β-DG. In skeletal muscle, DG is part of the dystrophin-glycoprotein complex that is crucial for sarcolemma stability and it is involved in a plethora of muscular dystrophy phenotypes. Due to the important role played by DG in skeletal muscle stability as well as in...
Article
Full-text available
Dystroglycan (DG) is a highly glycosylated protein complex that links the cytoskeleton with the extracellular matrix, mediating fundamental physiological functions such as mechanical stability of tissues, matrix organization and cell polarity. A crucial role in the glycosylation of the DG α subunit is played by its own N-terminal region that is req...
Data
Distribution of the centers of masses of S6 domains: In the crystallographic models of the WT and the three mutants (represented by spheres) and in the respective CORAL models (represented by dots) respect to the Ig-like domain and its center of mass (represented by mesh). (TIF)
Data
Guinier plots. Guinier plot representation of the SAXS data. The straight lines are the fitted data according to Guinier approximation to determine the radius of gyration and the scattering amplitude. A) V72I, B) D109N and C) T190M. (TIF)
Data
Comparison of the structural models of the WT and the three pathological mutants of α-DG-Nt. Typical CORAL models (green, red, blue and violet cartoon representations for the folded Ig-like and S6 domains, spheres for the restored missing fragments of WT (A), V72I (B), D109N (C) and T190M (D), respectively) overlaid to the respective CORAL models,...
Data
Additional SAXS structural parameters: Radius of gyration (Rg), maximum dimension (Dmax), Porod volume (A3), and MW (Da). Dmax was obtained from the p(r) distribution using GNOM; I(0) (scattering intensity) was obtained from the scattering data by the Guinier analysis. Molecular mass (Mr) was estimated from comparison with I(0) intensity of the sta...
Data
Sequence alignments. Inter-specific alignments in the regions spanning the amino acid positions: A) 65–110 and B) 187–221, referring to the murine Ig-like domain of α-DG. Accession codes for dystroglycan sequences: Homo sapiens (q14118), Macaca mulatta (f6ru72), Pan troglodytes (h2qml8), Gorilla gorilla gorilla (g3r897), Callitrix jacchus (f6trx4),...
Data
Electrostatic potential maps of V72I (A) and WT (B). The electrostatic potential (in kbT/ec units) is mapped on solvent-accessible surface of the WT and V72I pathological mutant accessible surfaces. Negative potential is colored in blue, positive potential in red. Color scale varies between -2 and +2. Molecular models (stretch 105–116) are represen...
Data
Thermal denaturation assay using DSF with SYPRO dye. Comparison of averaged unfolding fluorescent curves with the respective error bars for WT (A), V72I (B), D109N (C) and T190M (D). The fitting Boltzmann function limited to the temperature region of interest (first transition) is shown. (TIF)
Data
Experimental SAXS curves measured at different concentration: A) V72I, B) D109N and C) T190M. The zoomed regions of these graphs at low angles are presented on the right column. (TIF)
Data
Overall parameters calculated from SAXS experiments. SAXS data collection and processing information. Parameters derived from SAXS analysis are also reported. (DOCX)
Data
Table S1. Multiple alignment of selected mammalian sequences of the N‐terminal region of α‐DG. Table S2. SAXS structural parameters. Figure S1. Electrostatic potential maps of ma‐DG‐Nt and ha‐DG‐Nt. Figure S2. Superimposition of the ha‐DG‐Nt and ma‐DG‐Nt selected regions. Figure S3. Amino acid differences between mouse and human α‐DG‐Nt mapped...
Article
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Dystroglycan (DG), composed of α and β subunits, belongs to the dystrophin-associated glycoprotein complex. α-DG is an extracellular matrix protein that undergoes a complex post-translational glycosylation process. The bifunctional glycosyltransferase like-acetylglucosaminyltransferase (LARGE) plays a crucial role in the maturation of α-DG, enablin...
Article
Dystroglycan (DG) serves as an adhesion complex linking the actin cytoskeleton to the extracellular matrix. DG is encoded by a single gene as a precursor, which is constitutively cleaved to form the α- and β-DG subunits. α-DG is a peripheral protein characterized by an extensive glycosylation that is essential to bind laminin and other extracellula...
Article
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Background: Dystroglycan (DG) is an adhesion receptor complex composed of two non-covalently associated subunits, transcribed from a single gene. The extracellular α-DG is highly and heterogeneously glycosylated and binds with high affinity to laminins, and the transmembrane β-DG binds intracellular dystrophin. Multiple cellular functions have bee...
Article
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Group II chaperonins are ATP-ases indispensable for the folding of many proteins that play a crucial role in Archaea and Eukarya. They display a conserved two-ringed assembly enclosing an internal chamber where newly translated or misfolded polypeptides can fold to their native structure. They are mainly hexadecamers, with each eight-membered ring...
Article
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One of the problems with 2DE is that proteins present in low amounts in a sample are usually not detected, since their signals are masked by the predominant proteins. The elimination of these abundant proteins is not a guaranteed solution to achieve the desired results. The main objective of this study was the comparison of common and simple method...
Article
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Basement membrane (BM) extracellular matrices are crucial for the coordination of different tissue layers. A matrix adhesion receptor that is important for BM function and stability in many mammalian tissues is the dystroglycan (DG) complex. This comprises the non-covalently-associated extracellular α-DG, that interacts with laminin in the BM, and...
Article
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In skeletal muscle, dystroglycan (DG) is the central component of the dystrophin-glycoprotein complex (DGC), a multimeric protein complex that ensures a strong mechanical link between the extracellular matrix and the cytoskeleton. Several muscular dystrophies arise from mutations hitting most of the components of the DGC. Mutations within the DG ge...
Article
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Insulin-Degrading-Enzyme (IDE) is a Zn2+-dependent peptidase highly conserved throughout evolution and ubiquitously distributed in mammalian tissues wherein it displays a prevalent cytosolic localization. We have recently demonstrated a novel Heat Shock Protein-like behaviour of IDE and its association with the 26S proteasome. In the present study,...
Article
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The severe dystroglycanopathy known as a form of limb-girdle muscular dystrophy (LGMD2P) is an autosomal recessive disease caused by the point mutation T192M in α-dystroglycan. Functional expression analysis in vitro and in vivo indicated that the mutation was responsible for a decrease in posttranslational glycosylation of dystroglycan, eventually...
Article
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Dystrophin is a cytosolic protein belonging to a membrane-spanning glycoprotein complex, called dystrophin-glycoprotein complex (DGC) that is expressed in many tissues, especially in skeletal muscle and in the nervous system. The DGC connects the cytoskeleton to the extracellular matrix and, although none of the proteins of the DGC displays kinase...
Article
We generated a novel monoclonal antibody, DAG-6F4, against alpha-dystroglycan which immunolabels the sarcolemma in human muscle biopsies. Its seven amino-acid epitope, PNQRPEL, was identified using phage-displayed peptides and is located immediately after the highly-glycosylated mucin domain of alpha-dystroglycan. On Western blots of recombinant al...
Article
Dystroglycan is a member of the glycoprotein complex associated to dystrophin and composed by two subunits, the β-DG, a transmembrane protein, and the α-DG, an extensively glycosylated extracellular protein. The β-DG ectodomain degradation by the matrix metallo-proteinases (i.e. MMP-2 and MMP-9), in both pathological and physiological conditions, h...
Article
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A missense amino acid mutation of valine to aspartic acid in 567 position of alpha-dystroglycan (DG), identified in dag1-mutated zebrafish, results in a reduced transcription and a complete absence of the protein. Lacking experimental structural data for zebrafish DG domains, the detailed mechanism for the observed mutation-induced destabilization...
Article
The dystroglycan (DG) adhesion complex is formed by the peripheral α-DG and the transmembrane β-DG, both originating from the same precursor. α-DG plays a crucial role for tissue stability since it binds with high affinity a variety of proteins and proteoglycans in many different cell types. One common molecular feature of most of the α-DG ligands...
Poster
Alpha-dystroglycan (αDG) is an extracellular, glycosylated protein attached to the outer plasma membrane by its interaction with the transmembrane protein, beta-dystroglycan. Genetic mutations that alter the glycosylation state of αDG cause a number of inherited disorders, including Fukuyama MD and certain congenital and limb-girdle MDs. Many of th...
Article
Dystroglycan is a major adhesion complex composed of two subunits, α and β, that undergoes extensive post-translational modifications. In particular, its α subunit is heavily decorated with sugars, influencing its basement membrane binding properties. An altered glycosylation of α-dystroglycan is at the molecular basis of muscular dystrophies defin...
Article
Full-text available
Background α-Dystroglycan (α-DG) is heavily glycosylated within its central mucin-like domain. The glycosylation shell of α-dystroglycan is known to largely influence its functional properties toward extracellular ligands. The structural features of this α-dystroglycan domain have been poorly studied so far. For the first time, we have attempted a...
Article
Dystroglycan (DG) is a membrane-associated protein complex formed by two noncovalently linked subunits, α-DG, a highly glycosylated extracellular protein, and β-DG, a transmembrane protein. The interface between the two DG subunits, which is crucial to maintain the integrity of the plasma membrane, involves the C-terminal domain of α-DG and the N-t...
Article
Full-text available
Epitope tags and fluorescent fusion proteins have become indispensable molecular tools for studies in the fields of biochemistry and cell biology. The knowledge collected on the subdomain organization of the two subunits of the adhesion complex dystroglycan (DG) enabled us to insert the 10 amino acids myc-tag at different locations along the α-subu...
Article
Full-text available
Dystroglycan (DG) is an extracellular receptor composed of two subunits, α-DG and β-DG, connected through the α-DG C-terminal domain and the β-DG N-terminal domain. We report an alanine scanning of all DG cysteine residues performed on DG-GFP constructs overexpressed in 293-Ebna cells, demonstrating that Cys-669 and Cys-713, both located within the...
Article
DAG1 encodes for a precursor protein that liberates the two subunits featured by the dystroglycan (DG) adhesion complex that are involved in an increasing number of cellular functions in a wide variety of cells and tissues. Aside from the proteolytic events producing the α and β subunits, especially the former undergoes extensive "post-production"...
Article
Missense mutations in the SGCE gene encoding ε-sarcoglycan account for approximately 15% of SGCE-positive cases of myoclonus-dystonia syndrome (MDS) in humans. In this study, we show that while the majority of MDS-associated missense mutants modeled with a murine ε-sarcoglycan cDNA are substrates for endoplasmic reticulum-associated degradation, on...
Article
We observed a three-generation family with two maternal cousins and an uncle affected by mental retardation (MR) with cerebellar hypoplasia. X-linked inheritance and the presence of cerebellar malformation suggested a mutation in the OPHN1 gene. In fact, mutational screening revealed a 2-bp deletion that abolishes a donor splicing site, resulting i...
Article
Full-text available
The dystroglycan (DG) expression pattern can be altered in severe muscular dystrophies. In fact, some congenital muscular dystrophies (CMDs) and limb-girdle muscular dystrophies (LGMDs) are caused by point mutations identified in six glycosyltransferase genes which are likely to target different steps along the posttranslational "O-glycosylation ro...
Article
Dystroglycan (DG) is a cell surface receptor which is composed of two subunits that interact noncovalently, namely α- and β-DG. In skeletal muscle, DG is the central component of the dystrophin-glycoprotein complex (DGC) that anchors the actin cytoskeleton to the extracellular matrix. To date only the three-dimensional structure of the N-terminal r...
Article
Full-text available
Purpose. To report one case of corneal antibiotic deposition after ciprofloxacin administration in Laser Assisted Subepithelial Keratomileusis (LASEK). Methods. One case of post-LASEK treatment resulted in corneal precipitates and poor wound healing. Debris was analyzed with dark field microscopy and placed on a blood-agar plate seeded with a susce...
Article
Dystroglycan (DG) is a membrane receptor belonging to the complex of glycoproteins associated to dystrophin. DG is formed by two subunits, alpha-DG, a highly glycosylated extracellular matrix protein, and beta-DG, a transmembrane protein. The two DG subunits interact through the C-terminal domain of alpha-DG and the N-terminal extracellular domain...
Article
The interaction between a-dystroglycan (alpha-DG) and beta-dystroglycan (beta-DG), the two constituent subunits of the adhesion complex dystroglycan, is crucial in maintaining the integrity of the dystrophin-glycoprotein complex. The importance of the alpha-beta interface can be seen in the skeletal muscle of humans affected by severe conditions, s...
Article
We report the case of a congenital myasthenic syndrome due to a mutation in AGRN, the gene encoding agrin, an extracellular matrix molecule released by the nerve and critical for formation of the neuromuscular junction. Gene analysis identified a homozygous missense mutation, c.5125G>C, leading to the p.Gly1709Arg variant. The muscle-biopsy specime...
Article
During the last 15 years, following its identification and first detailed molecular characterization, the dystroglycan (DG) complex has taken centre stage in biology and biomedicine. Functions in different cells and tissues have been identified for this complex, ranging from its typical role in skeletal muscle as a sarcolemmal stabilizer, highlight...