Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Preliminary crystallographic analysis of the N-terminal PDZ-like domain of periaxin, an abundant peripheral nerve protein linked to human neuropathies.

ABSTRACT: Periaxin (PRX) is an abundant protein in peripheral nerves and contains a predicted PDZ-like domain at its N-terminus. The large isoform, L-PRX, is required for the maintenance of myelin in the peripheral nervous system and its defects cause neurological disease. Here, the human periaxin PDZ-like domain was crystallized and X-ray diffraction data were collected to 2.85 Å resolution using synchrotron radiation. The crystal belonged to the primitive hexagonal space group P3121 or P3221, with unit-cell parameters a = b = 80.6, c = 81.0 Å, ? = 120° and either two or three molecules in the asymmetric unit. The structure of PRX will shed light on its poorly characterized function in the nervous system.

SUBMITTER: Han H

PROVIDER: S-EPMC3702330 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Preliminary crystallographic analysis of the N-terminal PDZ-like domain of periaxin, an abundant peripheral nerve protein linked to human neuropathies.

Han Huijong H Kursula Petri P

Acta crystallographica. Section F, Structural biology and crystallization communications 20130630 Pt 7

Periaxin (PRX) is an abundant protein in peripheral nerves and contains a predicted PDZ-like domain at its N-terminus. The large isoform, L-PRX, is required for the maintenance of myelin in the peripheral nervous system and its defects cause neurological disease. Here, the human periaxin PDZ-like domain was crystallized and X-ray diffraction data were collected to 2.85 Å resolution using synchrotron radiation. The crystal belonged to the primitive hexagonal space group P3121 or P3221, with unit- ...[more]

PMID: 23832213

Similar Datasets

Neuroinflammation in the peripheral nerve: Cause, modulator, or bystander in peripheral neuropathies?

Project description:The role of innate and adaptive inflammation as a primary driver or modifier of neuropathy in premorbidly normal nerves, and as a critical player in amplifying neuropathies of other known causes (e.g., genetic, metabolic) is incompletely understood and under-researched, despite unmet clinical need. Also, cellular and humoral components of the adaptive and innate immune system are substantial disease modifying agents in the context of neuropathies and, at least in some neuropathies, there is an identified tight interrelationship between both compartments of the immune system. Additionally, the quadruple relationship between Schwann cell, axon, macrophage, and endoneurial fibroblast, with their diverse membrane bound and soluble signalling systems, forms a distinct focus for investigation in nerve diseases with inflammation secondary to Schwann cell mutations and possibly others. Identification of key immunological effector pathways that amplify neuropathic features and associated clinical symptomatology including pain should lead to realistic and timely possibilities for translatable therapeutic interventions using existing immunomodulators, alongside the development of novel therapeutic targets.

| S-EPMC4832258 | biostudies-other

Immunotherapy in Peripheral Neuropathies.

Project description:Immunotherapy has been investigated in a small subset of peripheral neuropathies, including an acute one, Guillain-Barré syndrome, and 3 chronic forms: chronic inflammatory demyelinating polyradiculoneuropathy, multifocal motor neuropathy, and neuropathy associated with IgM anti-myelin-associated glycoprotein. Several experimental studies and clinical data are strongly suggestive of an immune-mediated pathogenesis. Either cell-mediated mechanisms or antibody responses to Schwann cell, compact myelin, or nodal antigens are considered to act together in an aberrant immune response to cause damage to peripheral nerves. Immunomodulatory treatments used in these neuropathies aim to act at various steps of this pathogenic process. However, there are many phenotypic variants and, consequently, there is a significant difference in the response to immunotherapy between these neuropathies, as well as a need to improve our knowledge and long-term management of chronic forms.

| S-EPMC4720673 | biostudies-literature

Animal models of peripheral neuropathies.

Project description:Peripheral neuropathies are common neurological diseases, and various animal models have been developed to study disease pathogenesis and test potential therapeutic drugs. Three commonly studied disease models with huge public health impact are diabetic peripheral neuropathy, chemotherapy-induced peripheral neuropathy, and human immunodeficiency virus-associated sensory neuropathies. A common theme in these animal models is the comprehensive use of pathological, electrophysiological, and behavioral outcome measures that mimic the human disease. In recent years, the focus has shifted to the use of outcome measures that are also available in clinical use and can be done in a blinded and quantitative manner. One such evaluation tool is the evaluation of epidermal innervation with a simple skin biopsy. Future clinical trials will be needed to validate the translational usefulness of this outcome measure and validation against accepted outcome measures that rely on clinical symptoms or examination findings in patients.

| S-EPMC3337016 | biostudies-literature

Crystallization and preliminary crystallographic characterization of the N-terminal Kunitz domain of boophilin.

Project description:Boophilin is a tight-binding thrombin inhibitor composed of two canonical Kunitz-type domains in a tandem arrangement. Thrombin-bound boophilin can inhibit a second trypsin-like serine proteinase, most likely through the reactive loop of its N-terminal Kunitz domain. Here, the crystallization and preliminary crystallographic analysis of the isolated N-terminal domain of boophilin is reported. The crystals belonged to the orthorhombic space group P2(1)2(1)2(1) and diffracted to beyond 1.8 Å resolution using a sealed-tube home source and to 0.87 Å resolution at a synchrotron source.

| S-EPMC3325814 | biostudies-literature

Crystallographic anomalous diffraction data for the experimental phasing of two myelin proteins, gliomedin and periaxin.

Project description:We present datasets that can be used for the experimental phasing of crystal structures of two myelin proteins. The structures were recently described in the articles "Periaxin and AHNAK nucleoprotein 2 form intertwined homodimers through domain swapping" (H. Han, P. Kursula, 2014) [1] and "The olfactomedin domain from gliomedin is a β-propeller with unique structural properties" (H. Han, P. Kursula, 2015) [2]. Crystals of periaxin were derivatized with tungsten and xenon prior to data collection, and diffraction data for these crystals are reported at 3 and 1 wavelengths, respectively. Crystallographic data for two different pressurizing times for xenon are provided. Gliomedin was derivatized with platinum, and data for single-wavelength anomalous dispersion are included. The data can be used to repeat the phasing experiments, to analyze heavy atom binding sites in proteins, as well as to optimize future derivatization experiments of protein crystals with these and other heavy-atom compounds.

| S-EPMC5567927 | biostudies-literature

Expression of periaxin (PRX) specifically in the human cerebrovascular system: PDZ domain-mediated strengthening of endothelial barrier function.

Project description:Regulation of cerebral endothelial cell function plays an essential role in changes in blood-brain barrier permeability. Proteins that are important for establishment of endothelial tight junctions have emerged as critical molecules, and PDZ domain containing-molecules are among the most important. We have discovered that the PDZ-domain containing protein periaxin (PRX) is expressed in human cerebral endothelial cells. Surprisingly, PRX protein is not detected in brain endothelium in other mammalian species, suggesting that it could confer human-specific vascular properties. In endothelial cells, PRX is predominantly localized to the nucleus and not tight junctions. Transcriptome analysis shows that PRX expression suppresses, by at least 50%, a panel of inflammatory markers, of which 70% are Type I interferon response genes; only four genes were significantly activated by PRX expression. When expressed in mouse endothelial cells, PRX strengthens barrier function, significantly increases transendothelial electrical resistance (~35%; p < 0.05), and reduces the permeability of a wide range of molecules. The PDZ domain of PRX is necessary and sufficient for its barrier enhancing properties, since a splice variant (S-PRX) that contains only the PDZ domain, also increases barrier function. PRX also attenuates the permeability enhancing effects of lipopolysaccharide. Collectively, these studies suggest that PRX could potentially regulate endothelial homeostasis in human cerebral endothelial cells by modulating inflammatory gene programs.

| S-EPMC6030167 | biostudies-literature

Mitotoxicity in distal symmetrical sensory peripheral neuropathies.

Project description:Chronic distal symmetrical sensory peripheral neuropathy is a common neurological complication of cancer chemotherapy, HIV treatment and diabetes. Although aetiology-specific differences in presentation are evident, the clinical signs and symptoms of these neuropathies are clearly similar. Data from animal models of neuropathic pain suggest that the similarities have a common cause: mitochondrial dysfunction in primary afferent sensory neurons. Mitochondrial dysfunction is caused by mitotoxic effects of cancer chemotherapeutic drugs of several chemical classes, HIV-associated viral proteins, and nucleoside reverse transcriptase inhibitor treatment, as well as the (possibly both direct and indirect) effects of excess glucose. The mitochondrial injury results in a chronic neuronal energy deficit, which gives rise to spontaneous nerve impulses and a compartmental neuronal degeneration that is first apparent in the terminal receptor arbor--that is, intraepidermal nerve fibres--of cutaneous afferent neurons. Preliminary data suggest that drugs that prevent mitochondrial injury or improve mitochondrial function could be useful in the treatment of these conditions.

| S-EPMC4870000 | biostudies-literature

Contribution of Skin Biopsy in Peripheral Neuropathies.

Project description:In the last three decades the study of cutaneous innervation through 3 mm-punch-biopsy has provided an important contribution to the knowledge of small fiber somatic and autonomic neuropathies but also of large fiber neuropathies. Skin biopsy is a minimally invasive technique with the advantage, compared to sural nerve biopsy, of being suitable to be applied to any site in our body, of being repeatable over time, of allowing the identification of each population of nerve fiber through its target. In patients with symptoms and signs of small fiber neuropathy the assessment of IntraEpidermal Nerve Fiber density is the gold standard to confirm the diagnosis while the quantification of sudomotor, pilomotor, and vasomotor nerve fibers allows to evaluate and characterize the autonomic involvement. All these parameters can be re-evaluated over time to monitor the disease process and to evaluate the effectiveness of the treatments. Myelinated fibers and their receptors can also be evaluated to detect a "dying back" neuropathy early when nerve conduction study is still normal. Furthermore, the morphometry of dermal myelinated fibers has provided new insight into pathophysiological mechanisms of different types of inherited and acquired large fibers neuropathies. In genetic neuropathies skin biopsy has become a surrogate for sural nerve biopsy, no longer necessary in the diagnostic process, to study genotype-phenotype correlations.

| S-EPMC7765344 | biostudies-literature

Expression, purification and preliminary crystallographic studies of the C-terminal SH3 domain of human Tks4.

Project description:The Src homology 3 (SH3) domain is a small, noncatalytic domain with a conserved sequence of about 60 amino-acid residues that interacts with proline-rich peptides to form a protein complex. In this study, the C-terminal SH3 domain of human Tks4 (residues 853-911) was expressed, purified and crystallized. X-ray diffraction data were collected to 2.3 Å resolution. The crystal belonged to the trigonal space group P3121 (or P3221), with unit-cell parameters a = b = 83.87, c = 108.44 Å, α = β = 90, γ = 120°. Calculating the self-rotation and the native Patterson function did not lead to the detection of any noncrystallographic translational symmetry. Six, seven or eight protein molecules are likely to be present in the asymmetric unit, resulting in a Matthews coefficient and approximate solvent content of 2.71 Å(3) Da(-1) and 55%, 2.32 Å(3) Da(-1) and 47%, and 2.03 Å(3) Da(-1) and 39%, respectively. To solve the crystal structure of the C-terminal SH3 domain of human Tks4, the isomorphous replacement method is presently being utilized.

| S-EPMC3944698 | biostudies-literature

Preliminary crystallographic analysis of the N-terminal domain of FILIA, a protein essential for embryogenesis.

Project description:FILIA is a component of the subcortical maternal complex that is essential for early stage embryogenesis. Its 6xHis-tagged N-terminal domain was expressed in Escherichia coli and purified to homogeneity. Two types of crystals formed under different crystallization conditions during screening. Orthorhombic crystals appeared in a solution containing 1.4 M ammonium sulfate, 0.1 M Tris pH 8.2 and 12% glycerol, while tetragonal crystals were obtained using 15% PEG 4000 mixed with 0.1 M HEPES pH 7.5 and 15% 2-propanol. High-quality diffraction data were collected from the two crystal forms to resolutions of 1.8 and 2.2 A, respectively, using synchrotron radiation. The Matthews coefficients indicated that the P2(1)2(1)2(1) and P4(1)2(1)2 crystals contained two molecules and one molecule per asymmetric unit, respectively. A selenomethionine-substituted sample failed to crystallize under the native conditions, but another orthorhombic crystal form was obtained under different conditions and anomalous diffraction data were collected.

| S-EPMC2935241 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data