In: International journal of molecular sciences, 2017, vol. 18, no. 10, p. 2042
Microtubules are the main components of mitotic spindles, and are the pillars of the cellular cytoskeleton. They perform most of their cellular functions by virtue of their unique dynamic instability processes which alternate between polymerization and depolymerization phases. This in turn is driven by a precise balance between attraction and repulsion forces between the constituents of...
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In: International journal of molecular sciences, 2018, vol. 19, no. 2, p. 571
Alzheimer’s disease is the most fatal neurodegenerative disorder characterized by the aggregation and deposition of Amyloid β (Aβ) oligomers in the brain of patients. Two principal variants of Aβ exist in humans: Aβ1–40 and Aβ1–42. The former is the most abundant in the plaques, while the latter is the most toxic species and forms fibrils more rapidly. Interestingly, fibrils of...
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In: International journal of molecular sciences, 2018, vol. 19, no. 8, p. 2151
The protein ataxin-3 contains a polyglutamine stretch that triggers amyloid aggregation when it is expanded beyond a critical threshold. This results in the onset of the spinocerebellar ataxia type 3. The protein consists of the globular N-terminal Josephin domain and a disordered C-terminal tail where the polyglutamine stretch is located. Expanded ataxin-3 aggregates via a two-stage...
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In: Pharmaceuticals, 2018, vol. 11, no. 1, p. 22
The Toll-Like Receptor 7 (TLR7) is an endosomal membrane receptor involved in the innate immune system response. Its best-known small molecule activators are imidazoquinoline derivatives such as imiquimod (R-837) and resiquimod (R-848). Recently, an interaction between R-837 and the colchicine binding site of tubulin was reported. To investigate the possibility of an interaction between...
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In: Pharmaceutics, 2019, vol. 11, no. 11, p. 576
Physico-chemical properties of lactose are key factors in adhesive mixtures used as dry powder inhaler (DPI). Despite the abundant literature on this topic, the effect of the polymorphism and pseudo-polymorphism of lactose has been seldom investigated and discussed although often lactose used in DPI is subjected to unit operations, which may alter its solid-state properties. Here, we studied...
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In: DNA and cell biology
Hunter’s syndrome (mucopolysaccharidosis type II) is a rare X-linked lysosomal storage disorder caused by mutations in the iduronate 2-sulfatase (IDS) gene. Motivated by the case of a child affected by this syndrome, we compared the intracellular fate of wild type IDS (IDSWT) and of four nonsense mutations of IDS (IDSL482X, IDSY452X, IDSR443X and IDSW337X) generating progressively shorter ...
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In: Trends in biochemical sciences, 2019, vol. 44, no. 7, p. 589-598
Upon recognition of an antigen, the differentiation of antigen-inexperienced naïve T lymphocytes into subsets able to effectively coordinate host defense is controlled by a network of transcription factors and regulatory molecules. In the cell nucleus, these factors act in the context of epigenetic modifications that influence DNA accessibility and ultimately gene expression. This review...
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In: Critical reviews in biochemistry and molecular biology, 2019, vol. 54, no. 2, p. 153-163
About 40% of the eukaryotic cell’s proteins are inserted co- or post-translationally in the endoplasmic reticulum (ER), where they attain the native structure under the assistance of resident molecular chaperones and folding enzymes. Subsequently, these proteins are secreted from cells or are transported to their sites of function at the plasma membrane or in organelles of the secretory and ...
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In: Cell host & microbe, 2019, vol. 26, no. 5, p. p. 623-637.e8
Potent and broadly neutralizing antibodies (bnAbs) are the hallmark of HIV-1 protection by vaccination. The membrane-proximal external region (MPER) of the HIV-1 gp41 fusion protein is targeted by the most broadly reactive HIV-1 neutralizing antibodies. Here, we examine the structural and molecular mechansims of neutralization by anti-MPER bnAb, LN01, which was isolated from lymph-node-derived...
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In: Nature communications, 2019, vol. 10, p. 5058
The endoplasmic reticulum (ER) produces about 40% of the nucleated cell’s proteome. ER size and content in molecular chaperones increase upon physiologic and pathologic stresses on activation of unfolded protein responses (UPR). On stress resolution, the mammalian ER is remodeled to pre-stress, physiologic size and function on activation of the LC3-binding activity of the translocon...
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