scholarly journals Epistatic interactions can moderate the antigenic effect of substitutions in hemagglutinin of influenza H3N2 virus

2018 ◽  
Author(s):  
Björn F. Koel ◽  
David F. Burke ◽  
Stefan van der Vliet ◽  
Theo M. Bestebroer ◽  
Guus F. Rimmelzwaan ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Context Dependence ◽  
Single Amino Acid ◽  
H3n2 Virus ◽  
Amino Acid Substitutions ◽  
Epistatic Interactions ◽  
Context Dependent ◽  
The Impact ◽  
Influenza H3n2

AbstractWe previously showed that single amino acid substitutions at seven positions in hemagglutinin determined major antigenic change of influenza H3N2 virus. Here, the impact of two such substitutions was tested in eleven representative H3 hemagglutinins to investigate context-dependence effects. The antigenic effect of substitutions introduced at hemagglutinin position 145 was fully independent of the amino acid context of the representative hemagglutinins. Antigenic change caused by substitutions introduced at hemagglutinin position 155 was variable and context-dependent. Our results suggest that epistatic interactions with contextual amino acids in the hemagglutinin can moderate the magnitude of antigenic change.

scholarly journals Identification of separate domains in the adenovirus E1A gene for immortalization activity and the activation of virus early genes.

1986 ◽  
Vol 6 (10) ◽  
pp. 3470-3480 ◽  
Author(s):  
E Moran ◽  
B Zerler ◽  
T M Harrison ◽  
M B Mathews
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Point Mutations ◽  
Apparent Molecular Weight ◽  
Amino Acid Position ◽  
Cysteine Residue ◽  
Transformation Function ◽  
Single Amino Acid ◽  
Amino Acid Substitutions ◽  
E1a Gene

The transformation and early adenovirus gene transactivation functions of the E1A region were analyzed with deletion and point mutations. Deletion of amino acids from position 86 through 120 had little effect on the lytic or transforming functions of the E1A products, while deletion of amino acids from position 121 through 150 significantly impaired both functions. The sensitivity of the transformation function to alterations in the region from amino acid position 121 to 150 was further indicated by the impairment of transforming activity resulting from single amino acid substitutions at positions 124 and 135. Interestingly, conversion of a cysteine residue at position 124 to glycine severely impaired the transformation function without affecting the early adenovirus gene activating functions. Single amino acid substitutions in a different region of the E1A gene had the converse effect. All the mutants produced polypeptides of sufficient stability to be detected by Western immunoblot analysis. The single amino acid substitutions at positions 124 and 135, although impairing the transformation functions, did not detectably alter the formation of the higher-apparent-molecular-weight forms of the E1A products.

scholarly journals Analysis of Large-Scale Mutagenesis Data To Assess the Impact of Single Amino Acid Substitutions

Genetics ◽  
2017 ◽  
Vol 207 (1) ◽  
pp. 53-61 ◽  
Author(s):  
Vanessa E. Gray ◽  
Ronald J. Hause ◽  
Douglas M. Fowler
Keyword(s):  
Amino Acid ◽  
Large Scale ◽  
Single Amino Acid ◽  
Amino Acid Substitutions ◽  
The Impact

Identification of separate domains in the adenovirus E1A gene for immortalization activity and the activation of virus early genes

1986 ◽  
Vol 6 (10) ◽  
pp. 3470-3480
Author(s):  
E Moran ◽  
B Zerler ◽  
T M Harrison ◽  
M B Mathews
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Point Mutations ◽  
Apparent Molecular Weight ◽  
Amino Acid Position ◽  
Cysteine Residue ◽  
Transformation Function ◽  
Single Amino Acid ◽  
Amino Acid Substitutions ◽  
E1a Gene

The transformation and early adenovirus gene transactivation functions of the E1A region were analyzed with deletion and point mutations. Deletion of amino acids from position 86 through 120 had little effect on the lytic or transforming functions of the E1A products, while deletion of amino acids from position 121 through 150 significantly impaired both functions. The sensitivity of the transformation function to alterations in the region from amino acid position 121 to 150 was further indicated by the impairment of transforming activity resulting from single amino acid substitutions at positions 124 and 135. Interestingly, conversion of a cysteine residue at position 124 to glycine severely impaired the transformation function without affecting the early adenovirus gene activating functions. Single amino acid substitutions in a different region of the E1A gene had the converse effect. All the mutants produced polypeptides of sufficient stability to be detected by Western immunoblot analysis. The single amino acid substitutions at positions 124 and 135, although impairing the transformation functions, did not detectably alter the formation of the higher-apparent-molecular-weight forms of the E1A products.

Use of a deletion approach to assess the amino acid requirements for optimum fermentation by mixed micro-organisms from the sheep rumen

2003 ◽  
Vol 76 (1) ◽  
pp. 147-153 ◽  
Author(s):  
C. Atasoglu ◽  
A.Y. Guliye ◽  
R.J. Wallace
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Growth Yield ◽  
Gas Production ◽  
Single Amino Acid ◽  
Ruminal Fermentation ◽  
Isoleucine Leucine ◽  
Fatty Acid Production ◽  
Micro Organisms ◽  
The Impact

AbstractAmino acids stimulate the growth rate and growth yield of ruminal micro-organisms, but the basis of this stimulation, in terms of amino acids which most limit growth, has never been fully established. Here, for the first time, a deletion approach was investigated using in vitro incubations of mixed ruminal micro-organisms supplied with a mixture of xylose, starch and cellobiose as energy sources and ammonia plus a complete amino acids mixture or mixtures with a single amino acid omitted as nitrogen sources, enabling the evaluation of the impact on ruminal fermentation of the deletion of a single amino acid from a complete amino acids mixture. Significant effects (P < 0·05) on total gas production were observed after 10 h of incubation when glutamate, glutamine, isoleucine, leucine, phenylalanine, serine, tryptophan or tyrosine were deleted from the amino acids mixture. The only significant effect of an amino acid deletion on volatile fatty acid production at 10 h was with serine (P < 0·05), although the effect of omitting others, including arginine, isoleucine, leucine and phenylalanine, approached significance (P < 0·01). The removal of leucine caused a 0·09 decrease in growth yield (P < 0·05); no other deletion affected the yield significantly (P > 0·05). Net gas production for each treatment was calculated by subtracting gas production in the absence of carbohydrates from gas production in their presence, thus eliminating gas production from amino acids from the values. At all times up to 10 h, the most significant effects on net gas production were found when serine, leucine, or the aromatic amino acids were omitted from the amino acids mixture. Thus, the deletion approach confirmed that no single amino acid limits ruminal fermentation more than any other, although a few, principally phenylalanine, leucine and serine, have a particularly significant rôle in the ruminal fermentation rate of soluble, rapidly degraded materials and/or microbial growth efficiency.

The Impact of Single Amino Acid Substitutions in CD3γ on the CD3ϵγ Interaction and T-Cell Receptor–CD3 Complex Formation

2006 ◽  
Vol 67 (8) ◽  
pp. 579-588 ◽  
Author(s):  
E.A.J. Thomassen ◽  
E.H.A. Dekking ◽  
A. Thompson ◽  
K.L. Franken ◽  
Ö. Sanal ◽  
...  
Keyword(s):  
Amino Acid ◽  
T Cell ◽  
Complex Formation ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Single Amino Acid ◽  
Amino Acid Substitutions ◽  
The Impact

scholarly journals α-Helix E of Spo0A Is Required for σA- but Not for σH-Dependent Promoter Activation in Bacillus subtilis

2004 ◽  
Vol 186 (4) ◽  
pp. 1078-1083 ◽  
Author(s):  
Amrita Kumar ◽  
James A. Brannigan ◽  
Charles P. Moran
Keyword(s):  
Amino Acids ◽  
Bacillus Subtilis ◽  
Amino Acid ◽  
Rna Polymerase ◽  
Sigma Factor ◽  
Dna Binding Protein ◽  
Single Amino Acid ◽  
Amino Acid Substitutions ◽  
Promoter Activation ◽  
Α Helix

ABSTRACT At the onset of endospore formation in Bacillus subtilis, the DNA binding protein Spo0A activates transcription from two types of promoters. The first type includes the spoIIG and spoIIE promoters, which are used by σA-RNA polymerase, whereas the second type includes the spoIIA promoter, which is used by RNA polymerase containing the secondary sigma factor σH. Previous genetic analyses have identified specific amino acids in α-helix E of Spo0A that are important for activation of Spo0A-dependent, σA-dependent promoters. However, these amino acids are not required for activation of the σH-dependent spoIIA promoter. We now report the effects of additional single-amino-acid substitutions and the effects of deletions in α-helix E. The effects of alanine substitutions revealed one new position (239) in Spo0A that appears to be specifically required for activation of the σA-dependent promoters. Based on the effects of a deletion mutation, we suggest that α-helix E in Spo0A is not directly involved in interaction with σH-RNA polymerase.

scholarly journals Evidence for Modified Mechanisms of Chloroethene Oxidation in Pseudomonas butanovora Mutants Containing Single Amino Acid Substitutions in the Hydroxylase α-Subunit of Butane Monooxygenase

2007 ◽  
Vol 189 (14) ◽  
pp. 5068-5074 ◽  
Author(s):  
Kimberly H. Halsey ◽  
David M. Doughty ◽  
Luis A. Sayavedra-Soto ◽  
Peter J. Bottomley ◽  
Daniel J. Arp
Keyword(s):  
Amino Acid ◽  
Mutant Strain ◽  
Parent Compound ◽  
Single Amino Acid ◽  
Amino Acid Substitutions ◽  
Α Subunit ◽  
Mutant Strains ◽  
Pseudomonas Butanovora ◽  
Butane Monooxygenase ◽  
The Impact

ABSTRACT The properties of oxidation of dichloroethene (DCE) and trichloroethylene (TCE) by three mutant strains of Pseudomonas butanovora containing single amino acid substitutions in the α-subunit of butane monooxygenase hydroxylase (BMOH-α) were compared to the properties of the wild-type strain (Rev WT). The rates of oxidation of three chloroethenes (CEs) were reduced in mutant strain G113N and corresponded with a lower maximum rate of butane oxidation. The rate of TCE degradation was reduced by one-half in mutant strain L279F, whereas the rates of DCE oxidation were the same as those in Rev WT. Evidence was obtained that the composition of products of CE oxidation differed between Rev WT and some of the mutant strains. For example, while Rev WT released nearly all available chlorine stoichiometrically during CE oxidation, strain F321Y released about 40% of the chlorine during 1,2-cis-DCE and TCE oxidation, and strain G113N released between 14 and 25% of the available chlorine during oxidation of DCE and 56% of the available chlorine during oxidation of TCE. Whereas Rev WT, strain L279F, and strain F321Y formed stoichiometric amounts of 1,2-cis-DCE epoxide during oxidation of 1,2-cis-DCE, only about 50% of the 1,2-cis-DCE oxidized by strain G113N was detected as the epoxide. Evidence was obtained that 1,2-cis-DCE epoxide was a substrate for butane monooxygenase (BMO) that was oxidized after the parent compound was consumed. Yet all of the mutant strains released less than 40% of the available 1,2-cis-DCE chlorine, suggesting that they have altered activity towards the epoxide. In addition, strain G113N was unable to degrade the epoxide. TCE epoxide was detected during exposure of Rev WT and strain F321Y to TCE but was not detected with strains L279F and G113N. Lactate-dependent O2 uptake rates were differentially affected by DCE degradation in the mutant strains, providing evidence that some products released by the altered BMOs reduced the impact of CE on cellular toxicity. The use of CEs as substrates in combination with P. butanovora BMOH-α mutants might allow insights into the catalytic mechanism of BMO to be obtained.

scholarly journals Whole genomic analysis of two influenza H3N2 virus strains isolated from Qinghai, China

2019 ◽  
Author(s):  
Huaxiang Rao ◽  
Hong Li ◽  
Nannan Lu ◽  
Youju Lei ◽  
Shengcang Zhao ◽  
...  
Keyword(s):  
Hong Kong ◽  
Amino Acid ◽  
Vaccine Strain ◽  
Amino Acid Substitution ◽  
Antigenic Site ◽  
Influenza Viruses ◽  
H3n2 Virus ◽  
Amino Acid Substitutions ◽  
Qinghai Province ◽  
Influenza H3n2

Abstract Background Influenza H3N2 virus has a faster evolution rate than other types of influenza viruses. This study was performed to better understand the molecular evolution of influenza H3N2 in Qinghai Province, China in 2017.Methods Complete sequences of eight gene segments of two influenza H3N2 isolates in 2017 in Qinghai Province were sequenced and analyzed by MEGA 6.06 software.Results Phylogenetic analysis showed that two Qinghai H3N2 isolates were relatively close to the 2016–2017 vaccine strain, 3C.2a-A/Hong Kong/4801/2014. In HA protein, compared with the 2015-2016 WHO recommended vaccine strain A/Switzerland/971 5293/2013, six amino acid substitutions were observed in epitopes A and B in Qinghai isolates in 2017, however, only two amino acid substitutions were observed in epitopes A and B in Qinghai isolates compared with the A/Hong Kong/4801/2014, which indicated 2016-2017 vaccine strain might have a better protection against the strains circulating in Qinghai Province in 2017 . Besides, amino acid substitution of K160T at the glycosylation site of HA and H75P in PB1-F2 in the two Qinghai isolates might affect the antibodies binding ability and the virulence of influenza virus. And there was no key amino acid substitution in the key sites of segment NA, M, NP, NS, PA and PB2.Conclusions The presence of several antigenic site mutations in Qinghai H3N2 isolates confirms the evolution of circulating H3N2 strains. Enhancing the surveillance of influenza epidemic by whole genome sequencing is important to monitor whether the selected vaccine strains are protective against the circulating strains in Qinghai Province.

scholarly journals The CaaX Proteases, Afc1p and Rce1p, Have Overlapping but Distinct Substrate Specificities

2000 ◽  
Vol 20 (12) ◽  
pp. 4381-4392 ◽  
Author(s):  
Cynthia Evans Trueblood ◽  
Victor L. Boyartchuk ◽  
Elizabeth A. Picologlou ◽  
David Rozema ◽  
C. Dale Poulter ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Substrate Specificity ◽  
Single Amino Acid ◽  
In Vitro Assays ◽  
Sequence Motif ◽  
Amino Acid Substitutions ◽  
In The Wild

ABSTRACT Many proteins that contain a carboxyl-terminal CaaX sequence motif, including Ras and yeast a-factor, undergo a series of sequential posttranslational processing steps. Following the initial prenylation of the cysteine, the three C-terminal amino acids are proteolytically removed, and the newly formed prenylcysteine is carboxymethylated. The specific amino acids that comprise the CaaX sequence influence whether the protein can be prenylated and proteolyzed. In this study, we evaluated processing of a-factor variants with all possible single amino acid substitutions at either the a1, the a2, or the X position of the a-factor Ca1a2X sequence, CVIA. The substrate specificity of the two known yeast CaaX proteases, Afc1p and Rce1p, was investigated in vivo. Both Afc1p and Rce1p were able to proteolyze a-factor with A, V, L, I, C, or M at the a1 position, V, L, I, C, or M at the a2 position, or any amino acid at the X position that was acceptable for prenylation of the cysteine. Eight additional a-factor variants with a1 substitutions were proteolyzed by Rce1p but not by Afc1p. In contrast, Afc1p was able to proteolyze additional a-factor variants that Rce1p may not be able to proteolyze. In vitro assays indicated that farnesylation was compromised or undetectable for 11 a-factor variants that produced no detectable halo in the wild-type AFC1 RCE1 strain. The isolation of mutations in RCE1 that improved proteolysis of a-factor-CAMQ, indicated that amino acid substitutions E139K, F189L, and Q201R in Rce1p affected its substrate specificity.

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