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Evolutive Immunology: “How modular protein nanoparticles may expand the ability of subunit anti-viral vaccines: The spring viremia carp virus (SVCV) case”

Evolutive Immunology: “How modular protein nanoparticles may expand the ability of subunit anti-viral vaccines: The spring viremia carp virus (SVCV) case”

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https://doi.org/10.1016/j.fsi.2022.10.067 Abstract Spring viremia of carp (SVC) remains as a vaccine orphan disease mostly affecting juvenile specimens. Young fish are especially difficult to vaccinate and oral administration of vaccine combined with food would be the election system to minimise stress and the vaccination costs associated to injection. However, administration of prophylactics with food pellets faces off several drawbacks mainly related with vaccine degradation and weak protection correlates of oral vaccines. Here we present a platform based on recombinant proteins (subunit vaccines) manufactured as highly resistant nanostructured materials, and providing excellent levels of protection against SVC virus in a preliminary i.p injection challenge. The G3 domain of S...
Protein Folding and Conformational Diseases: “Exploring cryptic amyloidogenic regions in prion-like proteins from plants”

Protein Folding and Conformational Diseases: “Exploring cryptic amyloidogenic regions in prion-like proteins from plants”

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Front. Plant Sci., 16 January 2023Sec. Plant Proteomics and Protein Structural BiologyVolume 13 - 2022 | https://doi.org/10.3389/fpls.2022.1060410 Prion-like domains (PrLDs) are intrinsically disordered regions (IDRs) of low sequence complexity with a similar composition to yeast prion domains. PrLDs-containing proteins have been involved in different organisms’ regulatory processes. Regions of moderate amyloid propensity within IDRs have been shown to assemble autonomously into amyloid fibrils. These sequences tend to be rich in polar amino acids and often escape from the detection of classical bioinformatics screenings that look for highly aggregation-prone hydrophobic sequence stretches. We defined them as cryptic amyloidogenic regions (CARs) and recently developed an integrated
Nanobiotechnology: “Endosomal escape for cell-targeted proteins. Going out after going in”

Nanobiotechnology: “Endosomal escape for cell-targeted proteins. Going out after going in”

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Abstract Protein-based nanocarriers are versatile and biocompatible drug delivery systems. They are of particular interest in nanomedicine as they can recruit multiple functions in a single modular polypeptide. Many cell-targeting peptides or protein domains can promote cell uptake when included in these nanoparticles through receptor-mediated endocytosis. In that way, targeting drugs to specific cell receptors allows a selective intracellular delivery process, avoiding potential side effects of the payload. However, once internalized, the endo-lysosomal route taken by the engulfed material usually results in full degradation, preventing their adequate subcellular localization, bioavailability and subsequent therapeutic effect. Thus, entrapment into endo-lysosomes is a main bottlen...
11TH IBERIAN CONGRESS ON PRIONS | 11-12 MAY 2023

11TH IBERIAN CONGRESS ON PRIONS | 11-12 MAY 2023

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WELCOME Over 20 years have passed since the first case of BSE was diagnosed in Spain at the beginning of the century, an event that shaped many of our professional careers. Unfortunately, no treatment exists yet to fight the devastating fate of patients suffering from prion diseases, but since the “mad cow” crisis, formidable breakthroughs have happened in prion science. It is a field that has always embraced the one Health approach: bringing together multidisciplinary scientists to tackle one of the great unsolved challenges in science, to cure prion diseases, which share molecular mechanisms with other protein misfolding disorders of high prevalence in our aging society. With this in mind, Barcelona is proud to host the Iberian prion congress for the second time, a unique oppo
La resolució de l’estructura d’una proteïna amiloide funcional aporta noves claus sobre l’origen d’una malaltia rara

La resolució de l’estructura d’una proteïna amiloide funcional aporta noves claus sobre l’origen d’una malaltia rara

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Investigadors de la UAB han determinat l’estructura de les fibres amiloides de la proteïna hnRNPDL-2, implicada en la distròfia muscular de cintures tipus 3, utilitzant criomicroscòpia electrònica (crio-EM) d’alta resolució i han conclòs que la incapacitat de la proteïna per formar les fibres amiloides, i no l'agregació, seria la causa de la malaltia. Aquesta és la primera estructura amiloide determinada en alta resolució per un grup espanyol. El treball, publicat a Nature Communications, encamina el tractament cap a la cerca de molècules que estabilitzin o facilitin la formació de l’amiloide i obre la porta a estudiar amb la mateixa tècnica altres amiloides funcionals i les seves mutacions, per comprendre’n millor la implicació en la salut i en la malaltia. Els investigadors Javier Ga
Curs Nacional de Genètica 2023: Inscripcions obertes

Curs Nacional de Genètica 2023: Inscripcions obertes

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El Curs Nacional de Genètica (CNG 2023) és un esdeveniment anual organitzat per la Societat Espanyola de Genètica (SEG) que tindrà lloc del 13 al 17 de març a  Madrid. Sota el tema "Estructura, funció i evolució del genoma", l'esdeveniment reunirà experts en genètica, nacionals i internacionals,  per compartir avenços científics en el camp d’estudi. El programa del curs inclou conferències magistrals, així com tallers pràctics i sessions en què els participants podran presentar les seves pròpies investigacions i discutir idees amb altres professionals i estudiants interessats en el camp. Aurora Ruiz-Herrera, investigadora del grup d’Integritat i Inestabilitat del Genoma de l’IBB (UAB), i Lluis Montoliu, investigador del CSIC, coordinen aquests curs i en destaquen la im
Primer caso descrito de defectos genéticos asociados a la PPCDC, un enzima involucrado en la síntesis de la coenzima A

Primer caso descrito de defectos genéticos asociados a la PPCDC, un enzima involucrado en la síntesis de la coenzima A

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El coenzima A (CoA) es un cofactor esencial involucrado en una gran variedad de procesos metabólicos esenciales para la obtención de energía. Tanto eucariotas como procariotas sintetizan CoA a partir del pantotenato, conocido también como vitamina B5, mediante una vía metabólica casi universal. En humanos, esta vía implica cinco pasos enzimáticos que involucran cuatro enzimas: pantotenato quinasa (PANK), 4’-fosfopantotenoilcisteína sintetasa (PPCS), fosfopantotenoilcisteína descarboxilasa (PPCDC) y CoA sintasa (COASY). Hasta la fecha se conocían defectos genéticos en 3 de los 4 enzimas mencionados, siendo la excepción la PPCDC. En general, estos defectos daban lugar a una patología de carácter severo. La PPCDC codifica una cisteína descarboxilasa que utiliza flavin mononucleótido (FMN
L’estructura tridimensional del genoma en els mamífers, més diversa del que s’havia vist fins ara

L’estructura tridimensional del genoma en els mamífers, més diversa del que s’havia vist fins ara

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Un estudi liderat per investigadores de l'IBB i el Departament de Biologia Cel·lular, de Fisiologia i d’Immunologia  identifica diferents patrons de plegament tridimensional dels cromosomes al llarg de l’evolució dels mamífers i proporciona noves claus interpretatives sobre la plasticitat del genoma de les espècies. La investigación s'ha publicat a la revista Cell Reports. El genoma (el codi de la vida) no és només una seqüència lineal de lletres, sinó que està organitzat en forma de cromosomes i empaquetat de manera espacial dins les cèl·lules. Aquesta organització tridimensional és fonamental, ja que determina els gens que s’activen i desactiven en cada tipus cel·lular. Comparar les seqüències del genoma complet de diferents espècies permet estudiar la dinàmica evolutiva i la fun
Protein Folding and Conformational Diseases: “Development of a Highly Potent Transthyretin Amyloidogenesis Inhibitor: Design, Synthesis, and Evaluation”

Protein Folding and Conformational Diseases: “Development of a Highly Potent Transthyretin Amyloidogenesis Inhibitor: Design, Synthesis, and Evaluation”

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J. Med. Chem. 2022, 65, 21, 14673–14691Publication Date:October 28, 2022https://doi.org/10.1021/acs.jmedchem.2c01195 Abstract Transthyretin amyloidosis (ATTR) is a group of fatal diseases described by the misfolding and amyloid deposition of transthyretin (TTR). Discovering small molecules that bind and stabilize the TTR tetramer, preventing its dissociation and subsequent aggregation, is a therapeutic strategy for these pathologies. Departing from the crystal structure of TTR in complex with tolcapone, a potent binder in clinical trials for ATTR, we combined rational design and molecular dynamics (MD) simulations to generate a series of novel halogenated kinetic stabilizers. Among them, M-23 displays one of the highest affinities for TTR described so far. The TTR/M-23 crystal s
Protein Structure “Structural Basis for the SUMO2 Isoform Specificity of SENP7”

Protein Structure “Structural Basis for the SUMO2 Isoform Specificity of SENP7”

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Journal of Molecular Biology (JMB) Volume 434, Issue 24, 30 December 2022, 167875 https://doi.org/10.1016/j.jmb.2022.167875 Abstract SUMO proteases or deSUMOylases regulate the lifetime of SUMO-conjugated targets in the cell by cleaving off the isopetidic bond between the substrate and the SUMO modifier, thus reversing the conjugation activity of the SUMO E3 ligases. In humans the deSUMOylating activity is mainly conducted by the SENP/ULP protease family, which is constituted of six members sharing a homologous catalytic globular domain. SENP6 and SENP7 are the most divergent members of the family and they show a unique SUMO2/3 isoform preference and a particular activity for dismantling polySUMO2 chains. Here, we present the crystal structure of the catalytic domain of human SEN...