scholarly journals Charged Residues Flanking the Transmembrane Domain of Two Related Toxin–Antitoxin System Toxins Affect Host Response

Toxins ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 329
Author(s):  
Andrew Holmes ◽  
Jessie Sadlon ◽  
Keith Weaver
Keyword(s):  
Amino Acid ◽  
Enterococcus Faecalis ◽  
Host Response ◽  
Cytoplasmic Membrane ◽  
Transmembrane Domain ◽  
The Other ◽  
Type I ◽  
Transcriptomic Response ◽  
Specific Amino Acid ◽  
Transporter Protein

A majority of toxins produced by type I toxin–antitoxin (TA-1) systems are small membrane-localized proteins that were initially proposed to kill cells by forming non-specific pores in the cytoplasmic membrane. The examination of the effects of numerous TA-1 systems indicates that this is not the mechanism of action of many of these proteins. Enterococcus faecalis produces two toxins of the Fst/Ldr family, one encoded on pheromone-responsive conjugative plasmids (FstpAD1) and the other on the chromosome, FstEF0409. Previous results demonstrated that overexpression of the toxins produced a differential transcriptomic response in E. faecalis cells. In this report, we identify the specific amino acid differences between the two toxins responsible for the differential response of a gene highly induced by FstpAD1 but not FstEF0409. In addition, we demonstrate that a transporter protein that is genetically linked to the chromosomal version of the TA-1 system functions to limit the toxicity of the protein.

Covid-19 Mutations and How the Vaccine Enhances Immune Intelligence

2021 ◽  
Author(s):  
Xanya Sofra
Keyword(s):  
Amino Acid ◽  
Viral Entry ◽  
Open Reading Frames ◽  
Spike Protein ◽  
Single Amino Acid ◽  
Immune Memory ◽  
Type I ◽  
Specific Amino Acid ◽  
Adaptive Efficiency ◽  
Acid Exchange

We traced the coronavirus classification and evolution, analyzed the Covid-19 composition and its distinguishing characteristics when compared to SARS-CoV and MERS-CoV. Despite their close kinship, SARS-CoV and Covid-19 display significant structural differences, including 380 amino acid substitutions, and variable homology between certain open reading frames that are bound to diversify the pathogenesis and virulence of the two viral compounds. A single amino acid substitution such as replacing Aspartate (D) with Glycine (G) composes the D614G mutation that is around 20% more infectious than its predecessor 614D. The B117 variant, that exhibits a 70% transmissibility rate, harbours 23 mutants, each reflecting one amino acid exchange. We examined several globally spreading mutations, 501.V2, B1351, P1, and others, with respect to the specific amino acid conversions involved. Unlike previous versions of coronavirus, where random mutations eventually precipitate extinction, the multiplicity of over 300,000 mutations appears to have rendered Covid-19 more contagious, facilitating its ability to evade detection, thus challenging the effectiveness of a large variety of emerging vaccines. Vaccination enhances immune memory and intelligence to combat or obstruct viral entry by generating antibodies that will prohibit the cellular binding and fusion with the Spike protein, ultimately debilitating the virus from releasing its contents into the cell. Developing antibodies during the innate response, appears to be the most compelling solution in light of the hypothesis that Covid-19 inhibits the production of Interferon type I, compromising adaptive efficiency to recognize the virus, possibly provoking a cytokine storm that injures vital organs. With respect to that perspective, the safety and effectiveness of different vaccines is evaluated and compared, including the Spike protein mRNA version, the Adenovirus DNA, Spike protein subunits, the deactivated virus genres, or, finally, the live attenuated coronavirus that appears to demonstrate the greatest effectiveness, yet, encompass a relatively higher risk.

scholarly journals Determination of Peptide Contact Points in the Human Angiotensin II Type I Receptor (AT1) with Photosensitive Analogs of Angiotensin II

1999 ◽  
Vol 13 (4) ◽  
pp. 578-586 ◽  
Author(s):  
Stéphane A. Laporte ◽  
Antony A. Boucard ◽  
Guy Servant ◽  
Gaétan Guillemette ◽  
Richard Leduc ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Angiotensin Ii ◽  
Transmembrane Domain ◽  
At1 Receptor ◽  
High Yield ◽  
Type I ◽  
Terminal Amino Acid ◽  
Contact Points ◽  
Terminal Amino

Abstract To identify ligand-binding domains of Angiotensin II (AngII) type 1 receptor (AT1), two different radiolabeled photoreactive AngII analogs were prepared by replacing either the first or the last amino acid of the octapeptide by p-benzoyl-l-phenylalanine (Bpa). High yield, specific labeling of the AT1 receptor was obtained with the 125I-[Sar1,Bpa8]AngII analog. Digestion of the covalent 125I-[Sar1,Bpa8]AngII-AT1 complex with V8 protease generated two major fragments of 15.8 kDa and 17.8 kDa, as determined by SDS-PAGE. Treatment of the[ Sar1,Bpa8]AngII-AT1 complex with cyanogen bromide produced a major fragment of 7.5 kDa which, upon further digestion with endoproteinase Lys-C, generated a fragment of 3.6 kDa. Since the 7.5-kDa fragment was sensitive to hydrolysis by 2-nitro-5-thiocyanobenzoic acid, we circumscribed the labeling site of 125I-[Sar1,Bpa8]AngII within amino acids 285 and 295 of the AT1 receptor. When the AT1 receptor was photolabeled with 125I-[Bpa1]AngII, a poor incorporation yield was obtained. Cleavage of the labeled receptor with endoproteinase Lys-C produced a glycopeptide of 31 kDa, which upon deglycosylation showed an apparent molecular mass of 7.5 kDa, delimiting the labeling site of 125I-[Bpa1]AngII within amino acids 147 and 199 of the AT1 receptor. CNBr digestion of the hAT1 I165M mutant receptor narrowed down the labeling site to the fragment 166–199. Taken together, these results indicate that the seventh transmembrane domain of the AT1 receptor interacts strongly with the C-terminal amino acid of[ Sar1, Bpa8]AngII, whereas the N-terminal amino acid of[ Bpa1]AngII interacts with the second extracellular loop of the AT1 receptor.

THE RELATIONSHIP BETWEEN SOIL BACTERIA WITH SIMPLE NUTRITIONAL REQUIREMENTS AND THOSE REQUIRING AMINO ACIDS

1957 ◽  
Vol 3 (1) ◽  
pp. 73-80 ◽  
Author(s):  
T. M. B. Payne ◽  
J. W. Rouatt ◽  
A. G. Lochhead
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Soil Bacteria ◽  
Single Case ◽  
The Other ◽  
Nutritional Requirements ◽  
Soil Organisms ◽  
Specific Amino Acid ◽  
The Relationship ◽  
Maximum Development

Twenty-two of 30 representative soil bacteria having simple nutritional requirements, in that they showed maximum development in a medium of inorganic salts and sugar, were found to be able to synthesize a variety of amino acids, though in no single case were more than four ninhydrin-positive substances found. The culture filtrates permitted the growth of amino-acid-requiring bacteria to the extent that they contained the specific amino acid or acids required by strains of the latter group. The findings point to an associative action between these nutritional groups of soil organisms and suggest that the preferential stimulation in the rhizosphere of bacteria requiring amino acids may be ascribed in part to the ability of the other group of bacteria, which are numerically increased in the rhizosphere, to synthesize amino acids.

scholarly journals Steady-State Plasma Membrane Expression of Human Cytomegalovirus gB Is Determined by the Phosphorylation State of Ser900

1998 ◽  
Vol 72 (8) ◽  
pp. 6657-6664 ◽  
Author(s):  
Kenneth N. Fish ◽  
Cecilia Soderberg-Naucler ◽  
Jay A. Nelson
Keyword(s):  
Plasma Membrane ◽  
Steady State ◽  
Amino Acid ◽  
Human Cytomegalovirus ◽  
Transmembrane Domain ◽  
Signal Sequence ◽  
Amino Acid Type ◽  
Type I ◽  
Intracellular Compartments ◽  
U373 Cells

ABSTRACT Human cytomegalovirus (HCMV) infection of an astrocytoma cell line (U373) or human fibroblast (HF) cells results in a differential cell distribution of the major envelope glycoprotein gB (UL55). This 906-amino-acid type I glycoprotein contains an extracellular domain with a signal sequence, a transmembrane domain, and a 135-amino-acid cytoplasmic tail with a consensus casein kinase II (CKII) site located at Ser900. Since phosphorylation of proteins in the secretory pathway is an important determinant of intracellular trafficking, the state of gB phosphorylation in U373 and HF cells was examined. Analysis of cells expressing wild-type gB and gB with site-specific mutations indicated that the glycoprotein was equally phosphorylated at a single site, Ser900, in both U373 and HF cells. To assess the effect of charge on gB surface expression in U373 cells, Ser900 was replaced with an aspartate (Asp) or alanine (Ala) residue to mimic the phosphorylated and nonphosphorylated states, respectively. Expression of the Asp but not the Ala gB mutation resulted in an increase in the steady-state expression of gB at the plasma membrane (PM) in U373 cells. In addition, treatment of U373 cells with the phosphatase inhibitor tautomycin resulted in the accumulation of gB at the PM. Interestingly, the addition of a charge at Ser900 trapped gB in a low-level cycling pathway at the PM, preventing trafficking of the protein to thetrans-Golgi network or other intracellular compartments. Therefore, these results suggest that a tautomycin-sensitive phosphatase regulates cell-specific PM retrieval of gB to intracellular compartments.

scholarly journals Structure of human nucleosome containing the testis-specific histone variant TSH2B

2014 ◽  
Vol 70 (4) ◽  
pp. 444-449 ◽  
Author(s):  
Takashi Urahama ◽  
Naoki Horikoshi ◽  
Akihisa Osakabe ◽  
Hiroaki Tachiwana ◽  
Hitoshi Kurumizaka
Keyword(s):  
Crystal Structure ◽  
Amino Acid ◽  
Structural Changes ◽  
Structural Difference ◽  
Histone Variants ◽  
The Other ◽  
Human Testis ◽  
Amino Acid Residues ◽  
Histone H2b ◽  
Specific Amino Acid

The human histone H2B variant TSH2B is highly expressed in testis and may function in the chromatin transition during spermatogenesis. In the present study, the crystal structure of the human testis-specific nucleosome containing TSH2B was determined at 2.8 Å resolution. A local structural difference between TSH2B and canonical H2B in nucleosomes was detected around the TSH2B-specific amino-acid residue Ser85. The TSH2B Ser85 residue does not interact with H4 in the nucleosome, but in the canonical nucleosome the H2B Asn84 residue (corresponding to the TSH2B Ser85 residue) forms water-mediated hydrogen bonds with the H4 Arg78 residue. In contrast, the other TSH2B-specific amino-acid residues did not induce any significant local structural changes in the TSH2B nucleosome. These findings may provide important information for understanding how testis-specific histone variants form nucleosomes during spermatogenesis.

scholarly journals Mapping mutational effects along the evolutionary landscape of HIV envelope

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Hugh K Haddox ◽  
Adam S Dingens ◽  
Sarah K Hilton ◽  
Julie Overbaugh ◽  
Jesse D Bloom
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Long Range ◽  
The Other ◽  
Single Amino Acid ◽  
Specific Amino Acid ◽  
Viral Growth ◽  
Amino Acid Mutations ◽  
Hiv Envelope ◽  
Hiv Evolution

The immediate evolutionary space accessible to HIV is largely determined by how single amino acid mutations affect fitness. These mutational effects can shift as the virus evolves. However, the prevalence of such shifts in mutational effects remains unclear. Here, we quantify the effects on viral growth of all amino acid mutations to two HIV envelope (Env) proteins that differ at>100 residues. Most mutations similarly affect both Envs, but the amino acid preferences of a minority of sites have clearly shifted. These shifted sites usually prefer a specific amino acid in one Env, but tolerate many amino acids in the other. Surprisingly, shifts are only slightly enriched at sites that have substituted between the Envs—and many occur at residues that do not even contact substitutions. Therefore, long-range epistasis can unpredictably shift Env’s mutational tolerance during HIV evolution, although the amino acid preferences of most sites are conserved between moderately diverged viral strains.

scholarly journals Acute regulation of mouse AE2 anion exchanger requires isoform-specific amino acid residues from most of the transmembrane domain

2007 ◽  
Vol 584 (1) ◽  
pp. 59-73 ◽  
Author(s):  
A. K. Stewart ◽  
C. E. Kurschat ◽  
R. D. Vaughan-Jones ◽  
B. E. Shmukler ◽  
S. L. Alper
Keyword(s):  
Amino Acid ◽  
Anion Exchanger ◽  
Transmembrane Domain ◽  
Amino Acid Residues ◽  
Specific Amino Acid

scholarly journals The Ectodomains of rBAT and 4F2h Are Fake or Orphan α-Glucosidases

Molecules ◽  
2021 ◽  
Vol 26 (20) ◽  
pp. 6231
Author(s):  
Joana Fort ◽  
Adrià Nicolàs-Aragó ◽  
Manuel Palacín
Keyword(s):  
Amino Acid ◽  
Transmembrane Domain ◽  
The Other ◽  
Integrin Signaling ◽  
Amino Acid Transporters ◽  
Acid Transport ◽  
Transport Activity ◽  
Physiological Relevance ◽  
Covalently Linked ◽  
The Stability

It is known that 4F2hc and rBAT are the heavy subunits of the heteromeric amino acid transporters (HATs). These heavy subunits are N-glycosylated proteins, with an N-terminal domain, one transmembrane domain and a bulky extracellular domain (ectodomain) that belongs to the α-amylase family. The heavy subunits are covalently linked to a light subunit from the SLC7 family, which is responsible for the amino acid transport activity, forming a heterodimer. The functions of 4F2hc and rBAT are related mainly to the stability and trafficking of the HATs in the plasma membrane of vertebrates, where they exert the transport activity. Moreover, 4F2hc is a modulator of integrin signaling, has a role in cell fusion and it is overexpressed in some types of cancers. On the other hand, some mutations in rBAT are found to cause the malfunctioning of the b0,+ transport system, leading to cystinuria. The ectodomains of 4F2hc and rBAT share both sequence and structure homology with α-amylase family members. Very recently, cryo-EM has revealed the structure of several HATs, including the ectodomains of rBAT and 4F2hc. Here, we analyze available data on the ectodomains of rBAT and 4Fhc and their relationship with the α-amylase family. The physiological relevance of this relationship remains largely unknown.

Dual transcriptomics to determine interferon-gamma independent host response to intestinal Cryptosporidium parvum infection

2021 ◽  
Author(s):  
Gina M. Gallego-Lopez ◽  
Carolina Mendoza Cavazos ◽  
Andrés M. Tibabuzo Perdomo ◽  
Andrew L. Garfoot ◽  
Roberta M. O’Connor ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cryptosporidium Parvum ◽  
Chronic Infection ◽  
Host Response ◽  
Type I Interferon ◽  
Secondary Infection ◽  
Transcript Abundance ◽  
Type I ◽  
Transcriptomic Response ◽  
Dual Transcriptomics

Animals with a chronic infection of the parasite Toxoplasma gondii are protected against lethal secondary infection with other pathogens. Our group previously determined that soluble T. gondii antigens (STAg) can mimic this protection and be used as a treatment against several lethal pathogens. Because treatments are limited for the parasite Cryptosporidium parvum , we tested STAg as a C. parvum therapeutic. We determined that STAg treatment reduced C. parvum Iowa II oocyst shedding in IFNγ-KO mice. Murine intestinal sections were then sequenced to define the IFNγ independent transcriptomic response to C. parvum infection. Gene Ontology and transcript abundance comparisons showed host immune response and metabolism changes. Transcripts for type I interferon responsive genes were more abundant in C. parvum infected mice treated with STAg. Comparisons between PBS or STAg treatments showed no significant differences in C. parvum gene expression. C. parvum transcript abundance was highest in the ileum and mucin-like glycoproteins and the GDP-fucose transporter were among the most abundant. These results will assist the field in determining both host- and parasite-directed future therapeutic targets.

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