scholarly journals Does deamidation affect inhibitory mechanisms towards amyloid protein aggregation?

2020 ◽  
Vol 56 (68) ◽  
pp. 9787-9790
Author(s):  
Yuko P. Y. Lam ◽  
Cookson K. C. Chiu ◽  
Christopher A. Wootton ◽  
Ian Hands-Portman ◽  
Meng Li ◽  
...  
Keyword(s):  
Protein Aggregation ◽  
Amyloid Protein ◽  
Wild Type ◽  
Site Specific ◽  
Inhibitory Mechanisms ◽  
Specific Inhibitors

A diagram to show the differences between wild-type and deamidated hIAPPs interaction with site specific and non-specific inhibitors.

scholarly journals Functional expression of a yeast mitochondrial intron-encoded protein requires RNA processing at a conserved dodecamer sequence at the 3' end of the gene.

1989 ◽  
Vol 9 (4) ◽  
pp. 1507-1512 ◽  
Author(s):  
H Zhu ◽  
H Conrad-Webb ◽  
X S Liao ◽  
P S Perlman ◽  
R A Butow
Keyword(s):  
Genetic Analysis ◽  
Rna Processing ◽  
Fold Increase ◽  
Functional Expression ◽  
Rrna Gene ◽  
Yeast Mitochondria ◽  
Wild Type ◽  
Site Specific ◽  
Var1 Gene ◽  
A Site

All mRNAs of yeast mitochondria are processed at their 3' ends within a conserved dodecamer sequence, 5'-AAUAAUAUUCUU-3'. A dominant nuclear suppressor, SUV3-I, was previously isolated because it suppresses a dodecamer deletion at the 3' end of the var1 gene. We have tested the effects of SUV3-1 on a mutant containing two adjacent transversions within a dodecamer at the 3' end of fit1, a gene located within the 1,143-base-pair intron of the 21S rRNA gene, whose product is a site-specific endonuclease required in crosses for the quantitative transmission of that intron to 21S alleles that lack it. The fit1 dodecamer mutations blocked both intron transmission and dodecamer cleavage, neither of which was suppressed by SUV3-1 when present in heterozygous or homozygous configurations. Unexpectedly, we found that SUV3-1 completely blocked cleavage of the wild-type fit1 dodecamer and, in SUV3-1 homozygous crosses, intron conversion. In addition, SUV3-1 resulted in at least a 40-fold increase in the amount of excised intron accumulated. Genetic analysis showed that these phenotypes resulted from the same mutation. We conclude that cleavage of a wild-type dodecamer sequence at the 3' end of the fit1 gene is essential for fit1 expression.

Brain Targeting and Aβ Binding Bifunctional Nanoparticles Inhibit Amyloid Protein Aggregation in APP/PS1 Transgenic Mice

2021 ◽  
Author(s):  
Xiancheng Zhang ◽  
Xiaoyu Zhang ◽  
You Li ◽  
Manli Zhong ◽  
Pu Zhao ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Protein Aggregation ◽  
Brain Targeting ◽  
Amyloid Protein

scholarly journals Site-specific binding of wild-type p53 to cellular DNA is inhibited by SV40 T antigen and mutant p53.

1992 ◽  
Vol 6 (10) ◽  
pp. 1886-1898 ◽  
Author(s):  
J Bargonetti ◽  
I Reynisdottir ◽  
P N Friedman ◽  
C Prives
Keyword(s):  
Specific Binding ◽  
T Antigen ◽  
Mutant P53 ◽  
Wild Type ◽  
Sv40 T Antigen ◽  
Site Specific ◽  
Wild Type P53 ◽  
Cellular Dna

Fundamentals and Exploration of Aggregation-Induced Emission Molecules for Amyloid Protein Aggregation

2021 ◽  
Author(s):  
Yijing Tang ◽  
Dong Zhang ◽  
Yanxian Zhang ◽  
Yonglan Liu ◽  
Lirong Cai ◽  
...  
Keyword(s):  
Optical Properties ◽  
Protein Aggregation ◽  
Environmental Health ◽  
Amyloid Protein ◽  
Aggregation Induced Emission ◽  
The Past ◽  
Sensing Applications ◽  
Biomolecule Sensing

The past decade has witnessed the growing interest and advances in aggregation-induced emission (AIE) molecules as driven by their unique fluorescence/optical properties in particular sensing applications including biomolecule sensing/detection, environmental/health...

scholarly journals A Point Mutation in the mma3 Gene Is Responsible for Impaired Methoxymycolic Acid Production in Mycobacterium bovis BCG Strains Obtained after 1927

2000 ◽  
Vol 182 (12) ◽  
pp. 3394-3399 ◽  
Author(s):  
Marcel A. Behr ◽  
Benjamin G. Schroeder ◽  
Jacquelyn N. Brinkman ◽  
Richard A. Slayden ◽  
Clifton E. Barry
Keyword(s):  
Point Mutation ◽  
Mycobacterium Bovis ◽  
Mycobacterium Smegmatis ◽  
Pasteur Institute ◽  
Wild Type ◽  
Phenotypic Properties ◽  
Site Specific ◽  
Mutant Population ◽  
Mycolic Acids

ABSTRACT BCG vaccines are substrains of Mycobacterium bovisderived by attenuation in vitro. After the original attenuation (1908 to 1921), BCG strains were maintained by serial propagation in different BCG laboratories (1921 to 1961). As a result, various BCG substrains developed which are now known to differ in a number of genetic and phenotypic properties. However, to date, none of these differences has permitted a direct phenotype-genotype link. Since BCG strains differ in their abilities to synthesize methoxymycolic acids and since recent work has shown that the mma3 gene is responsible for O-methylation of hydroxymycolate precursors to form methoxymycolic acids, we analyzed methoxymycolate production andmma3 gene sequences for a genetically defined collection of BCG strains. We found that BCG strains obtained from the Pasteur Institute in 1927 and earlier produced methoxymycolates in vitro but that those obtained from the Pasteur Institute in 1931 and later all failed to synthesize methoxymycolates, and furthermore, themma3 sequence of the latter strains differs from that ofMycobacterium tuberculosis H37Rv by a point mutation at bp 293. Site-specific introduction of this guanine-to-adenine mutation into wild-type mma3 (resulting in the replacement of glycine 98 with aspartic acid) eliminated the ability of this enzyme to produce O-methylated mycolic acids when the mutant was cloned in tandem with mma4 into Mycobacterium smegmatis. These findings indicate that a point mutation in mma3 occurred between 1927 and 1931, and that this mutant population became the dominant clone of BCG at the Pasteur Institute.

scholarly journals Prohormone convertases 1/3 and 2 together orchestrate the site-specific cleavages of progastrin to release gastrin-34 and gastrin-17

2008 ◽  
Vol 415 (1) ◽  
pp. 35-43 ◽  
Author(s):  
Jens F. Rehfeld ◽  
Xiaorong Zhu ◽  
Christina Norrbom ◽  
Jens R. Bundgaard ◽  
Anders H. Johnsen ◽  
...  
Keyword(s):  
Structural Factors ◽  
Cleavage Sites ◽  
Wild Type ◽  
Prohormone Convertases ◽  
Site Specific ◽  
G Cells ◽  
Processing Site ◽  
Vitro Effect

Cellular synthesis of peptide hormones requires PCs (prohormone convertases) for the endoproteolysis of prohormones. Antral G-cells synthesize the most gastrin and express PC1/3, 2 and 5/6 in the rat and human. But the cleavage sites in progastrin for each PC have not been determined. Therefore, in the present study, we measured the concentrations of progastrin, processing intermediates and α-amidated gastrins in antral extracts from PC1/3-null mice and compared the results with those in mice lacking PC2 and wild-type controls. The expression of PCs was examined by immunocytochemistry and in situ hybridization of mouse G-cells. Finally, the in vitro effect of recombinant PC5/6 on progastrin and progastrin fragments containing the relevant dibasic cleavage sites was also examined. The results showed that mouse G-cells express PC1/3, 2 and 5/6. The concentration of progastrin in PC1/3-null mice was elevated 3-fold. Chromatography showed that cleavage of the Arg36Arg37 and Arg73Arg74 sites were grossly decreased. Accordingly, the concentrations of progastrin products were markedly reduced, α-amidated gastrins (-34 and -17) being 25% of normal. Lack of PC1/3 was without effect on the third dibasic site (Lys53Lys54), which is the only processing site for PC2. Recombinant PC5/6 did not cleave any of the dibasic processing sites in progastrin and fragments containing the relevant dibasic processing sites. The complementary cleavages of PC1/3 and 2, however, suffice to explain most of the normal endoproteolysis of progastrin. Moreover, the results show that PCs react differently to the same dibasic sequences, suggesting that additional structural factors modulate the substrate specificity.

scholarly journals Identification of the Telomere elongation mutation in Drosophila

2018 ◽  
Author(s):  
Hemakumar M. Reddy ◽  
Thomas A. Randall ◽  
Radmila Capkova Frydrychova ◽  
James M. Mason
Keyword(s):  
Drosophila Melanogaster ◽  
Next Generation Sequencing ◽  
Ltr Retrotransposons ◽  
Wild Type ◽  
Dominant Mutation ◽  
Site Specific ◽  
Site Specific Recombination ◽  
Telomere Elongation ◽  
Drosophila Genetic Reference Panel ◽  
Generation Sequencing

Background. Telomeres in Drosophila melanogaster are similar to those of other eukaryotes in terms of their function, although they are formed by non-LTR retrotransposons instead of telomerase-based short repeats. The length of the telomeres in Drosophila depends on the number of copies of these transposable elements. A dominant mutation, Tel1, causes a several-fold elongation of telomeres. Methods. In this study we identified the Tel1 mutation by a combination of transposon-induced, site-specific recombination and next generation sequencing. Results. Recombination located Tel1 to a 15 kb region in 92A. Comparison of the DNA sequence in this region with the Drosophila Genetic Reference Panel of wild type genomic sequences delimited Tel1 to a 3 bp deletion inside intron 8 of Ino80. Discussion. The mapped Tel1 mutation (3-bp deletion found in Ino80) did not appear to affect the quantity or length of the Ino80 transcript. Tel1 causes a significant reduction in transcripts of CG18493, a gene nested in an intron 8 of Ino80, which is expressed in ovaries and expected to encode a serine-type peptidase.

scholarly journals Developmental aspects of adipose tissue in GH receptor and prolactin receptor gene disrupted mice: site-specific effects upon proliferation, differentiation and hormone sensitivity

2006 ◽  
Vol 191 (1) ◽  
pp. 101-111 ◽  
Author(s):  
David J Flint ◽  
Nadine Binart ◽  
Stephanie Boumard ◽  
John J Kopchick ◽  
Paul Kelly
Keyword(s):  
Adipose Tissue ◽  
Receptor Gene ◽  
Metabolic Effects ◽  
Wild Type ◽  
Extrinsic Factors ◽  
Differentiation Potential ◽  
Site Specific ◽  
Proliferation And Differentiation

Direct metabolic effects of GH on adipose tissue are well established, but effects of prolactin (PRL) have been more controversial. Recent studies have demonstrated PRL receptors on adipocytes and effects of PRL on adipose tissue in vitro. The role of GH in adipocyte proliferation and differentiation is also controversial, since GH stimulates adipocyte differentiation in cell lines, whereas it stimulates proliferation but inhibits differentiation of adipocytes in primary cell culture. Using female gene disrupted (ko) mice, we showed that absence of PRL receptors (PRLRko) impaired development of both internal and s.c. adipose tissue, due to reduced numbers of adipocytes, an effect differing from that of reduced food intake, where cell volume is decreased. In contrast, GHRko mice exhibited major decreases in the number of internal adipocytes, whereas s.c. adipocyte numbers were increased, even though body weight was decreased by 40–50%. The changes in adipose tissue in PRLRko mice appeared to be entirely due to extrinsic factors since preadipocytes proliferated and differentiated in similar fashion to wild-type animals in vitro and their response to insulin and isoproterenol was similar to wild-type animals. This contrasted with GHRko mice, where s.c. adipocytes proliferated, differentiated, and responded to hormones in identical fashion to controls, whereas parametrial adipocytes exhibited markedly depressed proliferation and differentiation potential and failed to respond to insulin or noradrenaline. Our results provide in vivo evidence that both GH and PRL stimulate differentiation of adipocytes but that the effects of GH are site specific and induce intrinsic changes in the precursor population, which are retained in vitro.

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