scholarly journals The contribution of mutant amino acids to alloantigenicity.

1989 ◽  
Vol 170 (3) ◽  
pp. 739-750 ◽  
Author(s):  
J Bill ◽  
F Ronchese ◽  
R N Germain ◽  
E Palmer
Keyword(s):  
Amino Acid ◽  
Structural Model ◽  
Structure And Function ◽  
Single Amino Acid ◽  
Amino Acid Substitutions ◽  
Beta Chain ◽  
Alpha Helices ◽  
The Third ◽  
And Function ◽  
The Relationship

The I-Abm12 mutation has been used extensively to study the relationship between structure and function of murine class II major histocompatibility molecules. I-Abm12 differs from I-Ab by three amino acid replacements in the A beta chain, and the proposed structural model of the I-Abm12 molecule places these three amino acid substitutions along one of the alpha-helices where they may affect both antigen and TCR binding. Two of the substitutions, Ile----Phe67 and Thr----Lys71, are thought to point into the binding site, whereas the third substitution, Arg----Gln70, is thought to point up and hence, be available for binding to the TCR. These predicted orientations are consistent with serologic analysis of the bm12 molecule, which demonstrates that residue 70 is uniquely accessible to mAbs distinguishing I-Ab from I-Abm12. In this study we have determined the influence of each of these amino acid substitutions on the ability of the resulting molecules to stimulate a panel of I-Abm12 (allo) reactive T cell hybridomas. Our experiments indicate that reversion of the amino acid at position 70 from Gln (I-Abm12) to Arg (I-Ab) interferes with allorecognition by 33 of 35 I-Abm12-reactive hybridomas. On the other hand, many hybrids can tolerate amino acid substitutions at positions 67 or 71. Single amino acid substitutions at position 67, 70, or 71 are recognized by only a minority of I-Abm12-specific hybrids and usually the reactivity is greatly diminished. These data are most consistent with the idea that the amino acid at position 70 directly interacts with the TCR during allorecognition. The additional effects of residues 67 and 71 are consistent with a contribution by bound peptide to the allorecognition process.

scholarly journals Effects of single-point amino acid substitutions on the structure and function neuraminidase proteins in influenza A virus

2008 ◽  
Vol 52 (4) ◽  
pp. 216-223 ◽  
Author(s):  
Takuya Yano ◽  
Eri Nobusawa ◽  
Alexander Nagy ◽  
Setsuko Nakajima ◽  
Katsuhisa Nakajima
Keyword(s):  
Amino Acid ◽  
Influenza A Virus ◽  
Influenza A ◽  
Single Point ◽  
Structure And Function ◽  
Amino Acid Substitutions ◽  
And Function

scholarly journals Structure and Function of CC-Chemokine Receptor 5 Homologues Derived from Representative Primate Species and Subspecies of the Taxonomic Suborders Prosimii and Anthropoidea

2003 ◽  
Vol 77 (22) ◽  
pp. 12310-12318 ◽  
Author(s):  
Kevin J. Kunstman ◽  
Bridget Puffer ◽  
Bette T. Korber ◽  
Carla Kuiken ◽  
Una R. Smith ◽  
...  
Keyword(s):  
Amino Acid ◽  
Chemokine Receptor ◽  
Transmembrane Domain ◽  
Structure And Function ◽  
Primate Species ◽  
Amino Acid Substitutions ◽  
Immunodeficiency Virus ◽  
And Function ◽  
Cc Chemokine Receptor 5 ◽  
Hiv 1

ABSTRACT A chemokine receptor from the seven-transmembrane-domain G-protein-coupled receptor superfamily is an essential coreceptor for the cellular entry of human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV) strains. To investigate nonhuman primate CC-chemokine receptor 5 (CCR5) homologue structure and function, we amplified CCR5 DNA sequences from peripheral blood cells obtained from 24 representative species and subspecies of the primate suborders Prosimii (family Lemuridae) and Anthropoidea (families Cebidae, Callitrichidae, Cercopithecidae, Hylobatidae, and Pongidae) by PCR with primers flanking the coding region of the gene. Full-length CCR5 was inserted into pCDNA3.1, and multiple clones were sequenced to permit discrimination of both alleles. Compared to the human CCR5 sequence, the CCR5 sequences of the Lemuridae, Cebidae, and Cercopithecidae shared 87, 91 to 92, and 96 to 99% amino acid sequence homology, respectively. Amino acid substitutions tended to cluster in the amino and carboxy termini, the first transmembrane domain, and the second extracellular loop, with a pattern of species-specific changes that characterized CCR5 homologues from primates within a given family. At variance with humans, all primate species examined from the suborder Anthropoidea had amino acid substitutions at positions 13 (N to D) and 129 (V to I); the former change is critical for CD4-independent binding of SIV to CCR5. Within the Cebidae, Cercopithecidae, and Pongidae (including humans), CCR5 nucleotide similarities were 95.2 to 97.4, 98.0 to 99.5, and 98.3 to 99.3%, respectively. Despite this low genetic diversity, the phylogeny of the selected primate CCR5 homologue sequences agrees with present primate systematics, apart from some intermingling of species of the Cebidae and Cercopithecidae. Constructed HOS.CD4 cell lines expressing the entire CCR5 homologue protein from each of the Anthropoidea species and subspecies were tested for their ability to support HIV-1 and SIV entry and membrane fusion. Other than that of Cercopithecus pygerythrus, all CCR5 homologues tested were able to support both SIV and HIV-1 entry. Our results suggest that the shared structure and function of primate CCR5 homologue proteins would not impede the movement of primate immunodeficiency viruses between species.

scholarly journals Phenotypic Analysis of Random hnsMutations Differentiate DNA-Binding Activity from Properties offimA Promoter Inversion Modulation and Bacterial Motility

1999 ◽  
Vol 181 (3) ◽  
pp. 941-948 ◽  
Author(s):  
Gina M. Donato ◽  
Thomas H. Kawula
Keyword(s):  
Amino Acid ◽  
Dna Binding ◽  
Constitutive Expression ◽  
Binding Activity ◽  
Single Amino Acid ◽  
Amino Acid Substitutions ◽  
Phenotypic Analysis ◽  
Mutator Strain ◽  
Dna Binding Activity ◽  
And Function

ABSTRACT H-NS is a major Escherichia coli nucleoid-associated protein involved in bacterial DNA condensation and global modulation of gene expression. This protein exists in cells as at least two different isoforms separable by isoelectric focusing. Among other phenotypes, mutations in hns result in constitutive expression of theproU and fimB genes, increased fimApromoter inversion rates, and repression of the flhCDmaster operon required for flagellum biosynthesis. To understand the relationship between H-NS structure and function, we transformed a cloned hns gene into a mutator strain and collected a series of mutant alleles that failed to repress proUexpression. Each of these isolated hns mutant alleles also failed to repress fimB expression, suggesting that H-NS-specific repression of proU and fimBoccurs by similar mechanisms. Conversely, alleles encoding single amino acid substitutions in the C-terminal DNA-binding domain of H-NS resulted in significantly reduced affinity for DNA yet conferred a wild-type fimA promoter inversion frequency, indicating that the mechanism of H-NS activity in modulating promoter inversion is independent of DNA binding. Furthermore, two specific H-NS amino acid substitutions resulted in hypermotile bacteria, while C-terminal H-NS truncations exhibited reduced motility. We also analyzed H-NS isoform composition expressed by various hnsmutations and found that the N-terminal 67 amino acids were sufficient to support posttranslational modification and that substitutions at positions 18 and 26 resulted in the expression of a single H-NS isoform. These results are discussed in terms of H-NS domain organization and implications for biological activity.

scholarly journals Protein acetylation: an important mechanism in actinobacteria

2018 ◽  
Vol 38 (2) ◽  
Author(s):  
Huaidong Zhang ◽  
Ximing Xu
Keyword(s):  
Amino Acid ◽  
Structure And Function ◽  
Lysine Acetylation ◽  
Protein Acetylation ◽  
Research Article ◽  
Act Domain ◽  
Amino Acid Binding ◽  
Amino Acid Sensing ◽  
And Function ◽  
The Relationship

This is a commentary on the research article by Lu et al. recently published in Bioscience Reports. The GCN5-like acetyltransferases with amino acid-binding (ACT)-GCN5-related N-acetyltransferase (GNAT) domain organization have been identified in actinobacteria by Lu et al. (2017). The ACT domain is fused to the GNAT domain, conferring amino acid-induced allosteric regulation to these protein acetyltransferases (Pat) (amino acid sensing acetyltransferase (AAPatA)). Members of the AAPatA family share similar secondary structure and are divided into two groups based on the allosteric ligands of the ACT domain: the asparagine (Asn)-activated PatA and the cysteine (Cys)-activated PatA. The former are mainly found in Streptomyces; the latter are distributed in other actinobacteria. The authors investigated the effect of Asn and Cys on the acetylation activity of Sven_0867 (SvePatA, from Streptomyces venezuelae DSM 40230) and Amir_5672 (AmiPatA, from Actinosynnema mirum strain DSM 43827), respectively, as well as the relationship between the structure and function of these enzymes. Research history and progress on acetyltransferases and lysine acetylation of proteins were discussed. The activity of PatA and acetylation level of proteins may be closely correlated with intracellular concentrations of Asn and Cys in actinobacteria.

scholarly journals The Structure ofampGGene inPseudomonas aeruginosaand Its Effect on Drug Resistance

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Qingli Chang ◽  
Chongyang Wu ◽  
Chaoqing Lin ◽  
Peizhen Li ◽  
Kaibo Zhang ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Inhibitory Concentration ◽  
Normal Function ◽  
Structure And Function ◽  
Clinical Isolates ◽  
Site Specific ◽  
Directed Mutation ◽  
And Function ◽  
The Relationship

In order to study the relationship between the structure and function of AmpG, structure, site-specific mutation, and gene complementary experiments have been performed against the clinical isolates ofPseudomonas aeruginosa. We found that there are 51 nucleotide variations at 34 loci over theampGgenes from 24 of 35P. aeruginosastrains detected, of which 7 nucleotide variations resulted in amino acid change. TheampGvariants with the changed nucleotides (amino acids) could complement the function ofampGdeleted PA01 (PA01ΔG). The ampicillin minimum inhibitory concentration (MIC) of PA01ΔG complemented with 32ampGvariants was up to 512 μg/ml, similar to the original PA01 (P. aeruginosa PA01). Furthermore, site-directed mutation of two conservative amino acids (I53 and W90) showed that when I53 was mutated to 53S or 53T (I53S or I53T), the ampicillin MIC level dropped drastically, and the activity of AmpCβ-lactamase decreased as well. By contrast, the ampicillin MIC and the activity of AmpCβ-lactamase remained unchanged for W90R and W90S mutants. Our studies demonstrated that although nucleotide variations occurred in most of theampGgenes, the structure of AmpG protein in clinical isolates is stable, and conservative amino acid is necessary to maintain normal function of AmpG.

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