Signal sequence
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The low density lipoprotein receptor (LDLR) is a transmembrane protein that plays a key role in cholesterol metabolism. It contains 860 amino acids including a 21 amino acid long signal sequence, which directs the protein into the endoplasmic reticulum. Mutations in the LDLR gene lead to cholesterol accumulation in the plasma and results in familial hypercholesterolemia (FH). Knowledge of the impact of a mutation on the LDLR protein structure and function is very important for the diagnosis and management of FH. Unfortunately, for a large proportion of mutations this information is still missing. In this study, we focused on the LDLR signal sequence and carried out functional and in silico analyses of two sequence changes, p.(Gly20Arg) and p.(Leu15Pro), localized in this part of the LDLR. Our results revealed that the p.(Gly20Arg) change, previously described as disease causing, has no detrimental effect on protein expression or LDL particle binding. In silico analysis supports this observation, showing that both the wt and p.(Gly20Arg) signal sequences adopt an expected α-helix structure. In contrast, the mutation p.(Leu15Pro) is not associated with functional protein expression and exhibits a structure with disrupted a α-helical arrangement in the signal sequence, which most likely affects protein folding in the endoplasmic reticulum.
- MeSH
- arginin chemie MeSH
- CHO buňky MeSH
- Cricetulus MeSH
- endoplazmatické retikulum metabolismus MeSH
- glycin chemie MeSH
- heterozygot MeSH
- hyperlipoproteinemie typ II krev genetika MeSH
- konfokální mikroskopie MeSH
- křečci praví MeSH
- LDL-receptory genetika metabolismus MeSH
- leucin chemie MeSH
- lidé MeSH
- mutace MeSH
- prolin chemie MeSH
- proteiny - lokalizační signály genetika MeSH
- rodokmen MeSH
- sbalování proteinů MeSH
- sekundární struktura proteinů MeSH
- zvířata MeSH
- Check Tag
- křečci praví MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Sekvence FLAIR (Fluid Attenuated Inversion Recovery) je cíleně vyladěnou kombinací dvou odlišných sekvencí „Inversion Recovery" (IR) a Turbo Spin Echo (TSE), kterou proto označujeme IR-TSE. Tento vyšetřovací modus má parametry zvoleny tak, aby byla co nejvíce potlačena magnetizace mozkomíšního moku. Sekvence se ukázala velmi přínosnou při lokalizaci patologických procesů zvláště v blízkosti likvorových prostorů. Uvedený modus vyšetření užíváme s výhodou při podezření na demyelinizační onemocnění, k verifikaci diskrétních drobných ischemických ložisek a pozánětlivých změn. Užití této techniky se nabízí v celé řadě dalších indikací, kupříkladu mozkových metastáz nebo k verifikaci změn v CNS při klinickém podezření na tuberózní sklerózu.
FLAIR (Fluid Attenuated Inversion Recovery) belongs both to „Inversion Recovery" (IR) and Turbo Spin Echo (TSE) imaging modes. Therefore IR-TSE is another designation. The value of using FLAIR pulse sequences, with inversion times designed to cancel CSF signal while allowing recovery of most of the brain magnetization, was assessed. The pulse sequence proved to be beneficial in localizing lesions within the brain, especially in the vicinity of CSF spaces. We made use of our investigation protocol in the assessment of myelin disorders, discrete ischaemic lesions as well as inflammatory changes. There is a large field for the use of this technique in other indications as for example metastatic brain lesions or tuberous sclerosis to verify changes within the CNS.
The complete genome sequence of a severe isolate of broad bean true mosaic virus (genus Comovirus, subfamily Comovirinae, family Secoviridae) is presented. Comparison of the amino acid sequences of the capsid proteins and the polymerase showed striking differences to other comoviruses and highest similarities to legume-infecting comoviruses. Red clover mottle virus was recognized as the most similar virus with amino acid sequence identities ranging from 43 to 67% for individual genes.
Byly charakterizovány změny alfa subjednotek hlavních typů heterotrimerních GTP-vazebných (G) proteinů v CNS nebo imunitním systému po modulaci různými typy antidepresiv (TCA, SSRI) in vitro svyužitím linie C6 gliomových buněk a přirozených zabíječů (NK lymfocytů). Vlivem akutně působícího fluoxetinu byly sníženy hladiny G alfa q/11 subjednotky a 1, 4, 5 inositoltrifosfátu (IP3) jako druhého posla efektorové dráhy regulované fosfolipázou C až po apoptické děje. Byl prokázán vztah mezi profily Galfa subjednotek (G alfa q/11, G alfa s a G alfai1, 2) a typem antidepresiva, zvláště SSRI typu. Rovněž byl studován přenos buněčného signálu ve sledu purinoceptor (adenozinový receptor) – G protein – efektor a možný vztah k působení antidepresiva v modelových reakcích in vitro.
Changes of Galpha subunit levels of main heterotrimeric GTP-binding (G) proteins were characterized in CNS and immune system after antidepressant modulation in vitro using lines of C6 glioma cells and natural killers (NK lymphocytes). We analyzed cell signal transduction induced by acute effect of fluoxetine by decreased Galpha q/11 level and 1, 4, 5 inositoltriphosphate (IP3) as 2nd messenger of effector phospholipase C pathway and modulation of apoptosis. We demonstrated relationship among antidepressant especially of SSRI type and G alpha subunit patterns (G alfa q/11, G alfa s a G alfai1, 2) were demonstrated. Furthermore cell signal transduction via purinoceptor (adenosine receptor) – G protein – effector in relationship to antidepressant effect was studied in model reactions in vitro.
BACKGROUND: The classification of the Musaceae (banana) family species and their phylogenetic inter-relationships remain controversial, in part due to limited nucleotide information to complement the morphological and physiological characters. In this work the evolutionary relationships within the Musaceae family were studied using 13 species and DNA sequences obtained from a set of 19 unlinked nuclear genes. RESULTS: The 19 gene sequences represented a sample of ~16 kb of genome sequence (~73% intronic). The sequence data were also used to obtain estimates for the divergence times of the Musaceae genera and Musa sections. Nucleotide variation within the sample confirmed the close relationship of Australimusa and Callimusa sections and showed that Eumusa and Rhodochlamys sections are not reciprocally monophyletic, which supports the previous claims for the merger between the two latter sections. Divergence time analysis supported the previous dating of the Musaceae crown age to the Cretaceous/Tertiary boundary (~ 69 Mya), and the evolution of Musa to ~50 Mya. The first estimates for the divergence times of the four Musa sections were also obtained. CONCLUSIONS: The gene sequence-based phylogeny presented here provides a substantial insight into the course of speciation within the Musaceae. An understanding of the main phylogenetic relationships between banana species will help to fine-tune the taxonomy of Musaceae.
All grass species evolved from an ancestor that underwent a whole-genome duplication (WGD) approximately 70 million years ago. Interestingly, the short arms of rice chromosomes 11 and 12 (and independently their homologs in sorghum) were found to be much more similar to each other than other homeologous regions within the duplicated genome. Based on detailed analysis of rice chromosomes 11 and 12 and their homologs in seven grass species, we propose a mechanism that explains the apparently 'younger' age of the duplication in this region of the genome, assuming a small number of reciprocal translocations at the chromosome termini. In each case the translocations were followed by unbalanced transmission and subsequent lineage sorting of the involved chromosomes to offspring. Molecular dating of these translocation events also allowed us to date major chromosome 'fusions' in the evolutionary lineages that led to Brachypodium and Triticeae. Furthermore, we provide evidence that rice is exceptional regarding the evolution of chromosomes 11 and 12, inasmuch as in other species the process of sequence exchange between homeologous chromosomes ceased much earlier than in rice. We presume that random events rather than selective forces are responsible for the observed high similarity between the short arm ends of rice chromosomes 11 and 12.
- MeSH
- časové faktory MeSH
- chromozomy rostlin genetika MeSH
- druhová specificita MeSH
- duplikace genu MeSH
- fylogeneze MeSH
- genetická variace MeSH
- genom rostlinný genetika MeSH
- lipnicovité klasifikace genetika MeSH
- molekulární evoluce * MeSH
- molekulární sekvence - údaje MeSH
- rekombinace genetická MeSH
- sekvence nukleotidů MeSH
- sekvenční analýza DNA MeSH
- sekvenční homologie nukleových kyselin MeSH
- selekce (genetika) MeSH
- syntenie MeSH
- translokace genetická MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
Cyanobacteria are physiologically and morphologically diverse photosynthetic microbes that play major roles in the carbon and nitrogen cycles of the biosphere. Recently, they have gained attention as potential platforms for the production of biofuels and other renewable chemicals. Many cyanobacteria were characterized morphologically prior to the advent of genome sequencing. Here, we catalog cyanobacterial ultrastructure within the context of genomic sequence information, including high-magnification transmission electron micrographs that represent the diversity in cyanobacterial morphology. We place the image data in the context of tabulated protein domains-which are the structural, functional, and evolutionary units of proteins-from the 126 cyanobacterial genomes comprising the CyanoGEBA dataset. In particular, we identify the correspondence between ultrastructure and the occurrence of genes encoding protein domains related to the formation of cyanobacterial inclusions. This compilation of images and genome-level domain occurrence will prove useful for a variety of analyses of cyanobacterial sequence data and provides a guidebook to morphological features.
- MeSH
- bakteriální proteiny klasifikace genetika metabolismus MeSH
- fylogeneze MeSH
- genom bakteriální genetika MeSH
- genomika * MeSH
- proteinové domény MeSH
- sekvenční analýza DNA MeSH
- sinice * genetika ultrastruktura MeSH
- transmisní elektronová mikroskopie MeSH
- výpočetní biologie MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- srovnávací studie MeSH
Hepatitis B virus uses e antigen (HBe), which is dispensable for virus infectivity, to modulate host immune responses and achieve viral persistence in human hepatocytes. The HBe precursor (p25) is directed to the endoplasmic reticulum (ER), where cleavage of the signal peptide (sp) gives rise to the first processing product, p22. P22 can be retro-translocated back to the cytosol or enter the secretory pathway and undergo a second cleavage event, resulting in secreted p17 (HBe). Here, we report that translocation of p25 to the ER is promoted by translocon-associated protein complex. We have found that p25 is not completely translocated into the ER; a fraction of p25 is phosphorylated and remains in the cytoplasm and nucleus. Within the p25 sp sequence, we have identified three cysteine residues that control the efficiency of sp cleavage and contribute to proper subcellular distribution of the precore pool.
- MeSH
- cystein metabolismus MeSH
- endoplazmatické retikulum metabolismus MeSH
- hepatitida B - antigeny e * metabolismus MeSH
- hepatitida B * metabolismus MeSH
- lidé MeSH
- membránové glykoproteiny MeSH
- proteiny - lokalizační signály genetika MeSH
- proteiny vázající vápník MeSH
- receptory cytoplazmatické a nukleární MeSH
- receptory peptidů MeSH
- virus hepatitidy B metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The complete nucleotide sequence and genome organization of a hypovirus from the isolate ME711 of Phomopsis longicolla was determined and compared to sequences of members of the family Hypoviridae. The genome of the hypovirus, tentatively named Phomopsis longicolla hypovirus 1 (PlHV1-ME711), was determined to be 9760 nucleotides long, excluding the 3' poly (A) tail. The genome contains a single large open reading frame (ORF) encoding a polyprotein designated as P307. Its genomic organization is typical of members of the proposed genus Betahypovirus (Yaegashi et al. in Virus Res 165:143-50, 2012).
