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11.
The RicAFT (YmcA‐YlbF‐YaaT) complex carries two [4Fe‐4S]2+ clusters and may respond to redox changes
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Andrew W. Tanner Valerie J. Carabetta Ryan J. Martinie Ameya A. Mashruwala Jeffrey M. Boyd Carsten Krebs David Dubnau 《Molecular microbiology》2017,104(5):837-850
During times of environmental insult, Bacillus subtilis undergoes developmental changes leading to biofilm formation, sporulation and competence. Each of these states is regulated in part by the phosphorylated form of the master response regulator Spo0A (Spo0A~P). The phosphorylation state of Spo0A is controlled by a multi‐component phosphorelay. RicA, RicF and RicT (previously YmcA, YlbF and YaaT) have been shown to be important regulatory proteins for multiple developmental fates. These proteins directly interact and form a stable complex, which has been proposed to accelerate the phosphorelay. Indeed, this complex is sufficient to stimulate the rate of phosphotransfer amongst the phosphorelay proteins in vitro. In this study, we demonstrate that two [4Fe‐4S]2+ clusters can be assembled on the complex. As with other iron‐sulfur cluster‐binding proteins, the complex was also found to bind FAD, hinting that these cofactors may be involved in sensing the cellular redox state. This work provides the first comprehensive characterization of an iron‐sulfur protein complex that regulates Spo0A~P levels. Phylogenetic and genetic evidence suggests that the complex plays a broader role beyond stimulation of the phosphorelay. 相似文献
12.
J Klein J Gonzalez J Duchene L Esposito JP Pradère E Neau C Delage D Calise A Ahluwalia P Carayon JB Pesquero M Bader JP Schanstra JL Bascands 《FASEB journal》2009,23(1):134-142
Renal fibrosis is the common histological feature of advanced glomerular and tubulointerstitial disease leading to end-stage renal disease (ESRD). However, specific antifibrotic therapies to slow down the evolution to ESRD are still absent. Because persistent inflammation is a key event in the development of fibrosis, we hypothesized that the proinflammatory kinin B1 receptor (B1R) could be such a new target. Here we show that, in the unilateral ureteral obstruction model of renal fibrosis, the B1R is overexpressed and that delayed treatment with an orally active nonpeptide B1R antagonist blocks macrophage infiltration, leading to a reversal of the level of renal fibrosis. In vivo bone marrow transplantation studies as well as in vitro studies on renal cells show that part of this antifibrotic mechanism of B1R blockade involves a direct effect on resident renal cells by inhibiting chemokine CCL2 and CCL7 expression. These findings suggest that blocking the B1R is a promising antifibrotic therapy. 相似文献
13.
Background
DNA repair is the general term for the collection of critical mechanisms which repair many forms of DNA damage such as methylation or ionizing radiation. DNA repair has mainly been studied in experimental and clinical situations, and relatively few information-based approaches to new extracting DNA repair knowledge exist. As a first step, automatic detection of DNA repair proteins in genomes via informatics techniques is desirable; however, there are many forms of DNA repair and it is not a straightforward process to identify and classify repair proteins with a single optimal method. We perform a study of the ability of homology and machine learning-based methods to identify and classify DNA repair proteins, as well as scan vertebrate genomes for the presence of novel repair proteins. Combinations of primary sequence polypeptide frequency, secondary structure, and homology information are used as feature information for input to a Support Vector Machine (SVM). 相似文献14.
The pathway and targeting signal for delivery of the integral membrane glycoprotein LEP100 to lysosomes 总被引:6,自引:2,他引:4
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A complete set of chimeras was made between the lysosomal membrane glycoprotein LEP100 and the plasma membrane-directed vesicular stomatitis virus G protein, combining a glycosylated lumenal or ectodomain, a single transmembrane domain, and a cytosolic carboxyl-terminal domain. These chimeras, the parent molecules, and a truncated form of LEP100 lacking the transmembrane and cytosolic domains were expressed in mouse L cells. Only LEP100 and chimeras that included the cytosolic 11 amino acid carboxyl terminus of LEP100 were targeted to lysosomes. The other chimeras accumulated in the plasma membrane, and truncated LEP100 was secreted. Chimeras that included the extracellular domain of vesicular stomatitis G protein and the carboxyl terminus of LEP100 were targeted to lysosomes and very rapidly degraded. Therefore, in chimera-expressing cells, virtually all the chimeric molecules were newly synthesized and still in the biosynthesis and lysosomal targeting pathways. The behavior of one of these chimeras was studied in detail. After its processing in the Golgi apparatus, the chimera entered the plasma membrane/endosome compartment and rapidly cycled between the plasma membrane and endosomes before going to lysosomes. In pulse-expression experiments, a large population of chimeric molecules was observed to appear transiently in the plasma membrane by immunofluorescence microscopy. Soon after protein synthesis was inhibited, this surface population disappeared. When lysosomal proteolysis was inhibited, chimeric molecules accumulated in lysosomes. These data suggest that the plasma membrane/early endosome compartment is on the pathway to the lysosomal membrane. This explains why mutations that block endocytosis result in the accumulation of lysosomal membrane proteins in the plasma membrane. 相似文献
15.
Amino acid changes in the Sindbis virus E2 glycoprotein that increase neurovirulence improve entry into neuroblastoma cells. 总被引:1,自引:1,他引:0
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Sindbis virus (SV) is an alphavirus that causes encephalitis in mice and results in age-dependent mortality. The outcome is dependent on the virus strain. Residues at 55 and 172 in the E2 glycoprotein determine the neurovirulence for mice of different ages and the efficiency of replication in the nervous system and neuronal cells. To determine the effects of these two residues on the initial steps in replication, we studied viruses with a histidine or glutamine at E2 position 55 and a glycine or an arginine at position 172, E2[H55G172], E2[Q55G172], E2[H55R172], and E2[Q55R172]. The production of virus was detected earlier for viruses with a histidine at E2 position 55 in BHK-21 cells (4 to 6 versus 6 to 8 h) and for E2[H55G172] in N18 cells (6 versus 8 to 10 h). As shown previously, viruses with a glycine at E2 position 172 bound more efficiently to N18 cells and a histidine at E2 position 55 further improved binding only slightly. Viruses with E2[H55] exhibited more rapid internalization and degradation of viral proteins in both BHK-21 and N18 cells. Incubation of E2[H55G172] and E2[Q55G172] at various pHs and temperatures did not reveal differences in virion stability. These data suggest that the amino acids at E2 positions 172 and 55 affect both adsorption and penetration of SV and that these early steps in the replicative pathway contribute to increased neurovirulence. 相似文献
16.
JB Parentes-Vieira PV Lopes-Costa CG Pires AR dos Santos JD Pereira-Filho BB da Silva 《International Seminars in Surgical Oncology : ISSO》2007,4(1):22
Background
The objective of this study was to evaluate angiogenesis according to CD34 antigen expression in estrogen receptor (ER)-positive and negative breast carcinomas.Methods
This study comprised 64 cases of infiltrating ductal carcinoma in postmenopausal women divided into two groups: Group A: ER-positive, n = 35; and Group B: ER-negative, n = 29. The anti-CD34 monoclonal antibody was used as a marker for endothelial cells. Microvessel count was carried out in 10 fields per slide using a 40× objective lens (magnification 400×). Statistical analysis of the data was performed using Student's t-test (p < 0.05).Results
The mean number of vessels stained with the anti-CD34 antibody in the estrogen receptor-positive and negative tumors was 23.51 ± 1.15 and 40.24 ± 0.42, respectively. The number of microvessels was significantly greater in the estrogen receptor-negative tumors (p < 0.001).Conclusion
ER-negative tumors have significantly greater CD34 antigen expression compared to ER-positive tumors.17.
Comparison of protein patterns of Listeria monocytogenes grown in biofilm or in planktonic mode by proteomic analysis 总被引:1,自引:0,他引:1
Trémoulet F Duché O Namane A Martinie B Labadie JC;European Listeria Genome Consortium 《FEMS microbiology letters》2002,210(1):25-31
The proteome of a Listeria monocytogenes strain isolated from a food plant was investigated to study the differential protein pattern expressed by biofilms and planktonic bacteria. The approach used in this study was a combination of two-dimensional electrophoresis, matrix-assisted laser desorption ionization-time of flight and database searches for the protein identification. Thirty-one proteins varied significantly between the two growth conditions. Twenty-two and nine proteins were up- and down-regulated respectively and nine proteins were successfully identified. The variations of the protein patterns indicated that the biofilm development is probably controlled by specific regulation of protein expression involved at various levels of cellular physiology. 相似文献
18.
Substitution bias, rapid saturation, and the use of mtDNA for nematode systematics 总被引:13,自引:0,他引:13
Only relatively recently have researchers turned to molecular methods for
nematode phylogeny reconstruction. Thus, we lack the extensive literature
on evolutionary patterns and phylogenetic usefulness of different DNA
regions for nematodes that exists for other taxa. Here, we examine the
usefulness of mtDNA for nematode phylogeny reconstruction and provide data
that can be used for a priori character weighting or for parameter
specification in models of sequence evolution. We estimated the
substitution pattern for the mitochondrial ND4 gene from intraspecific
comparisons in four species of parasitic nematodes from the family
Trichostrongylidae (38-50 sequences per species). The resulting pattern
suggests a strong mutational bias toward A and T, and a lower
transition/transversion ratio than is typically observed in other taxa. We
also present information on the relative rates of substitution at first,
second, and third codon positions and on relative rates of saturation of
different types of substitutions in comparisons ranging from intraspecific
to interordinal. Silent sites saturate extremely quickly, presumably owing
to the substitution bias and, perhaps, to an accelerated mutation rate.
Results emphasize the importance of using only the most closely related
sequences in order to infer patterns of substitution accurately for
nematodes or for other taxa having strongly composition-biased DNA. ND4
also shows high amino acid polymorphism at both the intra- and
interspecific levels, and in higher level comparisons, there is evidence of
saturation at variable amino acid sites. In general, we recommend using
mtDNA coding genes only for phylogenetics of relatively closely related
nematode species and, even then, using only nonsynonymous substitutions and
the more conserved mitochondrial genes (e.g., cytochrome oxidases). On the
other hand, the high substitution rate in genes such as ND4 should make
them excellent for population genetics studies, identifying cryptic
species, and resolving relationships among closely related congeners when
other markers show insufficient variation.
相似文献
19.
Phylogeny of the Drosophila saltans species group based on combined analysis of nuclear and mitochondrial DNA sequences 总被引:2,自引:0,他引:2
Nucleotide sequences from two nuclear loci, alcohol dehydrogenase and
internal transcribed spacer-1 of the nuclear ribosomal DNA repeats, and two
mitochondrial genes, cytochrome oxidase I and cytochrome oxidase II, were
determined from nine species in the Drosophila saltans species group. The
partition homogeneity test and partitioned Bremer support were used to
measure incongruence between phylogenetic hypotheses generated from
individual partitions. Individual loci were generally congruent with each
other and consistent with the previously proposed morphological hypothesis,
although they differed in level of resolution. Since extreme conflict
between partitions did not exist, the data were combined and analyzed
simultaneously. The total evidence method gave a more resolved and highly
supported phylogeny, as indicated by bootstrap proportions and decay
indices, than did any of the individual analyses. The cordata and elliptica
subgroups, considered to have diverged early in the history of the D.
saltans group, were sister taxa to the remainder of the saltans group. The
sturtevanti subgroup, represented by D. milleri and D. sturtevanti,
occupies an intermediate position in this phylogeny. The saltans and
parasaltans subgroups are sister clades and occupy the most recently
derived portion of the phylogeny. As with previous morphological studies,
phylogenetic relationships within the saltans subgroup were not
satisfactorily resolved by the molecular data.
相似文献
20.
Nucleotide sequence comparisons were used to investigate the evolution of P
transposable elements and the possibility that horizontal transfer has
played a role in their occurrence in natural populations of Drosophila and
other Diptera. The phylogeny of P elements was examined using published
sequences from eight dipteran taxa and a new, partial sequence from
Scaptomyza elmoi. The results from a number of different analyses are
highly consistent and reveal a P-element phylogeny that contradicts the
phylogeny of the species. At least three instances of horizontal transfer
are necessary to explain this incongruence, but other explanations cannot
be ruled out at this time.
相似文献