Search results for "Macromolecular Substance"
showing 10 items of 882 documents
Mapping protein matrix cavities in human cytoglobin through Xe atom binding
2004
Abstract Cytoglobin is the fourth recognized globin type, almost ubiquitously distributed in human tissues; its function is still poorly understood. Cytoglobin displays a core region of about 150 residues, structurally related to hemoglobin and myoglobin, and two extra segments, about 20 residues each, at the N- and C-termini. The core region hosts a large apolar cavity, held to provide a ligand diffusion pathway to/from the heme, and/or ligand temporary docking sites. Here we report the crystal structure (2.4 A resolution, R -factor 19.1%) of a human cytoglobin mutant bearing the CysB2(38) → Ser and CysE9(83) → Ser substitutions (CYGB*), treated under pressurized xenon. Three Xe atoms bind…
Structure of the human filamin A actin-binding domain.
2009
Filamin A (FLNa) is a large dimeric protein that binds to actin filaments via its actin-binding domain (ABD). The crystal structure of this domain was solved at 3.2 A resolution. The domain adopts a closed conformation typical of other ABDs, but also forms a dimer both in crystallization conditions and in solution. The structure shows the localization of the residues mutated in patients with periventricular nodular heterotopia or otopalatodigital syndrome. Structural analysis predicts that mutations in both types of disorder may affect actin binding.
Effectiveness of cyclosporine A in patients with moderate to severe plaque psoriasis in a real-life clinical setting in Italy: the TRANSITION study
2020
Background: Cyclosporine A (CsA) is one of the systemic therapeutic options for moderate-to-severe psoriasis, based on its efficacy and rapidity of action. The current study investigated the response to CsA in patients with moderate-to-severe plaque psoriasis. Materials and Methods: TRANSITION was an observational, cross-sectional, multicentre study which evaluated the proportion of partial- and suboptimal-responders among patients with moderate-to-severe plaque psoriasis treated with continuous CsA for >= 12 weeks. Patients demonstrating a Psoriasis Area and Severity Index (PASI) response of >= 90, >= 75 and <90, >= 50 and <75 and <50 were defined as responders, subopt…
Dupilimab Efficacy in Patients with Uncontrolled, Moderate-to-Severe Asthma by Body Mass Index
2019
Introduction: Obesity is associated with increased asthma severity, poor asthma control, and poor response to inhaled corticosteroids. Dupilumab (DPL), a fully human monoclonal antibody blocks the shared receptor component for interleukin (IL)-4/IL-13, key drivers of type 2 inflammation. In the phase 3 QUEST trial (NCT02414854), add-on DPL 200/300 mg every 2 wks (q2w) vs placebo (PBO) reduced severe exacerbations and improved pre-bronchodilator (BD) FEV1 in patients (pts) with uncontrolled, moderate-to-severe asthma. Aim: To assess the effect of baseline (BL) body mass index (BMI) on DPL efficacy in uncontrolled, moderate-to-severe asthma pts. Methods: Annualized rate of severe exacerbation…
Identification and relevance of the CD95-binding domain in the N-terminal region of ezrin.
2003
The CD95 (Fas/APO-1) linkage to the actin cytoskeleton through ezrin is an essential requirement for susceptibility to the CD95-mediated apoptosis in CD4+ T cells. We have previously shown that moesin was not involved in the binding to CD95. Here we further support the specificity of the ezrin/CD95 binding, showing that radixin did not bind CD95. The ezrin region specifically and directly involved in the binding to CD95 was located in the middle lobe of the ezrin FERM domain, between amino acids 149 and 168. In this region, ezrin, radixin, and moesin show 60-65% identity, as compared with the 86% identity in the whole FERM domain. Transfection of two different human cell lines with a green …
MyRIP, a novel Rab effector, enables myosin VIIa recruitment to retinal melanosomes
2002
Defects of the myosin VIIa motor protein cause deafness and retinal anomalies in humans and mice. We report on the identification of a novel myosin-VIIa-interacting protein that we have named MyRIP (myosin-VIIa- and Rab-interacting protein), since it also binds to Rab27A in a GTP-dependent manner. In the retinal pigment epithelium cells, MyRIP, myosin VIIa and Rab27A are associated with melanosomes. In transfected PC12 cells, overexpression of MyRIP was shown to interfere with the myosin VIIa tail localization. We propose that a molecular complex composed of Rab27A, MyRIP and myosin VIIa bridges retinal melanosomes to the actin cytoskeleton and thereby mediates the local trafficking of thes…
Mutants of Saccharomyces cerevisiae cell division cycle defective in cytokinesis. Biosynthesis of the cell wall and morphology
1982
The four temperature-sensitive mutants of Saccharomyces cerevisiae in the cell division cycle defective in cytokinesis (cdc, 3, 10, 11 and 12), have been analyzed with respect to the biosynthesis of the cell wall polymers. After 3 hours of incubation at the non-permissive temperature (37 degrees C) these strains stop growing. The synthesis of glucan, mannan and chitin (wall polymers) level off in a similar time, but glucan, mannan and chitin synthases remained active for at least 4 hours. If the mutants are analyzed by transmission and scanning electron microscopy different pictures emerge. Two of the mutants cdc 10 and cdc 12, after 3 hours of incubation at 37 degrees C present apparently …
Topical Review: Progress in Desmin-Related Myopathies
2000
Desmin-related myopathies are sporadic and familial neuromuscular conditions of considerable clinical heterogeneity uniformly marked by the pathologic accretion of desmin, often in a filamentous fashion. A large variety of other proteins, some of them cytoskeletal, also accrue. Morphologically, two types may be distinguished, one characterized by inclusions such as cytoplasmic and spheroid bodies or desmin-dystrophin plaques and another marked by granulofilamentous material. The genetic spectrum of desmin-related myopathies is quite diverse in that missense mutations and deletions in the desmin gene and a missense mutation in the α-B crystallin gene have been detected and several genes on o…
Myogenesis and contraction in the early embryonic heart of the rainbow trout
1977
Myogenesis in the embryonic heart of the rainbow trout, Salmo galrdneri (Rich.), was investigated electron microscopically from the 29th to the 41st somite stage. Thick and thin myofilaments are formed simultaneously as well as precursors of Z-lines, to which the thin filaments are attached. The genesis of filaments takes place in the region around the intracellular yolk droplets. The first myofibrils appear by the 33rd somite stage, probably formed by a mechanism of self-assembly in which the binding sites of actin and myosin participate. A- and I-bands do not develop before the 38th somite stage. The contraction already begins during the 33rd somite stage in the middle of the tubular hear…
Evidence for Myosin VIIa-Driven Transport of Rhodopsin in the Plasma Membrane of the Photoreceptor-Connecting Cilium
2007
Defects in the gene encoding for the unconventional myosin VIIa leads to human Usher syndrome 1B, the most common form of hereditary combined blindness and deafness. To determine cellular function of myosin VIIa, we have investigated the subcellular localization of myosin VIIa in spacial relation relationship to potentially interacting proteins in mammalian photoreceptor cells. Western blot analysis of the axonemal fraction of photoreceptor cells by Western blot show that myosin VIIa and actin, as well as opsin, were present in the ciliary portion of the photoreceptors. Improved immunoelectron microscopy revealed that in mammalian photoreceptor cells, myosin VIIa was localized at the membra…