scholarly journals Novel biological implication of a strictly monomorphic GCC repeat in the human PRKACB gene

2021 ◽  
Author(s):  
Safoura Khamse ◽  
Zahra Jafarian ◽  
Ali Bozorgmehr ◽  
Mostafa Tavakoli ◽  
Hossein Afshar Iranian ◽  
...  
Keyword(s):  
Late Onset ◽  
Human Subjects ◽  
Three Dimensional ◽  
Dna Structure ◽  
Dimensional Structure ◽  
Protein Coding ◽  
Three Dimensional Structure ◽  
Significant Divergence ◽  
The Impact ◽  
The Brain

Abstract Across human protein-coding genes, PRKACB (Protein Kinase CAMP-Activated Catalytic Subunit Beta) contains one of the longest GCC-repeats, and is predominantly expressed in the brain. Here we studied this STR in 300 human subjects, consisting of late-onset neurocognitive disorder (NCD) (N = 150) and controls (N = 150). We also studied the impact of this STR on the three-dimensional structure of DNA. While the PRKACB GCC-STR was strictly monomorphic at 7-repeats, we detected two 7/8 genotypes only in the NCD group. In comparison to all other lengths, (GCC)7 had the least effect on the three-dimensional structure of DNA, evidenced by minimal divergence between 0 and 7-repeats (divergence score = 0.04) and significant divergence between 0 and 8 repeats (divergence score = 0.50). A similar inert effect to the GCC-repeat was not detected in other classes of STRs such as GA and CA repeats. In conclusion, we report monomorphism of an exceptionally long GCC repeat in the PRKACB gene in human, its inert effect on DNA structure, and divergence in two cases of late-onset NCD. This is the first indication of natural selection for an exceptionally long monomorphic GCC-repeat, which probably evolved to function as an “epigenetic knob”, without changing the regional DNA structure.

scholarly journals Novel implications of a strictly monomorphic (GCC) repeat in the human PRKACB gene

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Safoura Khamse ◽  
Zahra Jafarian ◽  
Ali Bozorgmehr ◽  
Mostafa Tavakoli ◽  
Hossein Afshar ◽  
...  
Keyword(s):  
Tandem Repeats ◽  
Late Onset ◽  
Core Promoter ◽  
Human Subjects ◽  
3D Structure ◽  
Three Dimensional ◽  
Dna Structure ◽  
Neuroprotective Effects ◽  
The Impact ◽  
The Brain

AbstractPRKACB (Protein Kinase CAMP-Activated Catalytic Subunit Beta) is predominantly expressed in the brain, and regulation of this gene links to neuroprotective effects against tau and Aβ-induced toxicity. Here we studied a (GCC)-repeat spanning the core promoter and 5′ UTR of this gene in 300 human subjects, consisting of late-onset neurocognitive disorder (NCD) (N = 150) and controls (N = 150). We also implemented several models to study the impact of this repeat on the three-dimensional (3D) structure of DNA. While the PRKACB (GCC)-repeat was strictly monomorphic at 7-repeats, we detected two 7/8 genotypes only in the NCD group. In all examined models, the (GCC)7 and its periodicals had the least range of divergence variation on the 3D structure of DNA in comparison to the 8-repeat periodicals and several hypothetical repeat lengths. A similar inert effect on the 3D structure was not detected in other classes of short tandem repeats (STRs) such as GA and CA repeats. In conclusion, we report monomorphism of a long (GCC)-repeat in the PRKACB gene in human, its inert effect on DNA structure, and enriched divergence in late-onset NCD. This is the first indication of natural selection for a monomorphic (GCC)-repeat, which probably evolved to function as an “epigenetic knob”, without changing the regional DNA structure.

scholarly journals Two Pathogenic Gene Mutations Identified Associating with Congenital Cataract and Iris Coloboma Respectively in a Chinese Family

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Bin Li ◽  
Bin Lu ◽  
Xuewen Guo ◽  
Shenghui Hu ◽  
Guihu Zhao ◽  
...  
Keyword(s):  
Congenital Cataract ◽  
Three Dimensional ◽  
Gene Mutations ◽  
Dimensional Structure ◽  
Chinese Family ◽  
Control Group ◽  
Three Dimensional Structure ◽  
Han Ethnicity ◽  
The Family ◽  
The Impact

Purpose. To screen out pathogenic genes in a Chinese family with congenital cataract and iris coloboma. Material and Methods. A three-generation family with congenital cataract and iris coloboma from a Han ethnicity was recruited. DNA was extracted from peripheral blood samples collected from all individuals in the family. Whole exon sequencing was employed for screening the disease-causing gene mutations in the proband, and Sanger sequencing was used for other members of the family and a control group of 500 healthy individuals. Bioinformatics analysis and three-dimensional structure predictions were used to predict the impact of amino acid changes on protein structure and function. Results. The candidate genes of cataract and iris coloboma were successfully screened out. A heterozygote mutation, CRYGD c.70C>A (p.P24T), was identified as cosegregating with congenital cataracts, while another heterozygous mutation, WFS1 c.1514G>C (p.C505S), which had not been reported previously, cosegregated with congenital iris coloboma. Bioinformatic analyses and three-dimensional structure prediction proved that the three-dimensional structures of WFS1 p.C505S and CRYGD p.P24T changed markedly and may contribute significantly to iris coloboma and congenital cataract, respectively. Conclusions. We report a novel mutation, WFS1 p.C505S, and a known mutation, CRYGD p.P24T, that cosegregate with iris coloboma and congenital cataract, respectively, in a Chinese family. This is the first time the association of WFS1 p.C505S with iris coloboma has been demonstrated, although CRYGD p.P24T has been widely reported as being associated with congenital cataract, especially in the Eastern Asian population. These findings may have future therapeutic benefit for the diagnosis of iris coloboma and congenital cataract. The results may also be relevant in further studies aiming to investigate the molecular pathogenesis of iris coloboma and congenital cataract.

Contrasting the temporal dynamics of stand structure in even- and uneven-sized Picea abies dominated stands

2011 ◽  
Vol 41 (2) ◽  
pp. 289-299 ◽  
Author(s):  
Eric K. Zenner ◽  
Erkki Lähde ◽  
Olavi Laiho
Keyword(s):  
Temporal Dynamics ◽  
Three Dimensional ◽  
Tree Size ◽  
Dimensional Structure ◽  
Diameter Distribution ◽  
Structural Development ◽  
Three Dimensional Structure ◽  
Single Tree ◽  
Single Tree Selection ◽  
The Impact

Although proposed as a means of increasing structural diversity in managed forests, the impact of single-tree selection on the temporal dynamics of three-dimensional structure has not been previously evaluated. Forest structural development in Picea-dominated stands was contrasted over 15 years in stem-mapped randomized plots in southern Finland that underwent either low thinning (creating the even-sized (ES) structure of a bell-shaped diameter distribution) or single-tree selection (maintaining the uneven-sized (UES) structure of a reverse-J-shaped distribution) through multiple harvest entries. Structure was quantified with nonspatial stand attributes (e.g., density) and indices that quantify spatially explicit relationships among neighboring trees (e.g., structural complexity index (SCI)). Over time, three-dimensional structure reflected differential tree growth and mortality, resulting in minor changes in tree composition, spatial pattern, and tree size differentiation and somewhat greater changes in the SCI. The third harvest entry simplified the forest structure in both structure types. However, structural metrics such as the variability of tree diameters, tree size differentiation, and the SCI recovered to preharvest levels within 2–4 years in UES plots, whereas no recovery was seen in the ES structure type. Single-tree selection was demonstrated to perpetuate the uneven-sized structure associated with natural nonpyrogenic Picea-dominated forests.

Modeling the impact of point mutations on the stability of proteins

2020 ◽  
Vol 18 (04) ◽  
pp. 2050019
Author(s):  
K. G. Kulikov ◽  
T. V. Koshlan
Keyword(s):  
Protein Interactions ◽  
Protein Complexes ◽  
Three Dimensional ◽  
Point Mutations ◽  
Dimensional Structure ◽  
Amino Acid Residues ◽  
Three Dimensional Structure ◽  
The Stability ◽  
The Impact ◽  
Proven Theorem

A new method has been introduced which allows us to determine the stability of protein complexes with point changes of amino acid residues that also take into account the three-dimensional structure of the complex. This formulated and proven theorem is aimed at determining the criterion for the stability of protein molecules. The algorithm and software package were developed for analyzing protein interactions, taking into account their three-dimensional structure from the PDB database.

Folding of the td pre-RNA with the help of the RNA chaperone StpA

2002 ◽  
Vol 30 (6) ◽  
pp. 1175-1180 ◽  
Author(s):  
O. Mayer ◽  
C. Waldsich ◽  
R. Grossberger ◽  
R. Schroeder
Keyword(s):  
Conformational Changes ◽  
Three Dimensional ◽  
Group I Intron ◽  
Dimensional Structure ◽  
Rna Chaperone ◽  
Three Dimensional Structure ◽  
Group I ◽  
The Impact

The td group I intron is inserted in the reading frame of the thymidylate synthase gene, which is mainly devoid of structural elements. In vivo, translation of the pre-mRNA is required for efficient folding of the intron into its splicing-competent structure. The ribosome probably resolves exon-intron interactions that interfere with splicing. Uncoupling splicing from translation, by introducing a non-sense codon into the upstream exon, reduces the splicing efficiency of the mutant pre-mRNA. Alternatively to the ribosome, co-expression of genes that encode proteins with RNA chaperone activity promote folding of the td pre-mRNA in vivo. These proteins also efficiently accelerate folding of the td pre-mRNA in vitro. In order to understand the mechanism of action of RNA chaperones, we probed the impact of the RNA chaperone StpA on the structure of the td intron in vivo and compared it with that of the well characterized Cyt-18 protein, which is a group-I-intron-specific splicing factor. We found that the two proteins have opposite effects on the structure of the td intron. While StpA loosens the three-dimensional structure, Cyt-18 tightens it up. Furthermore, mutations that destabilize the intron structure render the mutants sensitive to StpA, whereas splicing of these mutants is rescued by Cyt-18. Our results provide direct evidence for protein-induced conformational changes within a catalytic RNA in vivo. Whereas StpA resolves tertiary contacts enabling the RNA to refold, Cyt-18 contributes to the stabilization of the native three-dimensional structure.

The Three-dimensional structure of frozen-hydrated nudaurelia capensis β virus

1987 ◽  
Vol 45 ◽  
pp. 650-651
Author(s):  
N. H. Olson ◽  
T. S. Baker ◽  
Wu Bo Mu ◽  
J. E. Johnson ◽  
D. A. Hendry
Keyword(s):  
South African ◽  
Rna Virus ◽  
Carbon Film ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
Electron Dose ◽  
Total Electron ◽  
Three Dimensional Structure ◽  
Negative Stain ◽  
Dimensional Reconstruction

Nudaurelia capensis β virus (NβV) is an RNA virus of the South African Pine Emperor moth, Nudaurelia cytherea capensis (Lepidoptera: Saturniidae). The NβV capsid is a T = 4 icosahedron that contains 60T = 240 subunits of the coat protein (Mr = 61,000). A three-dimensional reconstruction of the NβV capsid was previously computed from visions embedded in negative stain suspended over holes in a carbon film. We have re-examined the three-dimensional structure of NβV, using cryo-microscopy to examine the native, unstained structure of the virion and to provide a initial phasing model for high-resolution x-ray crystallographic studiesNβV was purified and prepared for cryo-microscopy as described. Micrographs were recorded ∼1 - 2 μm underfocus at a magnification of 49,000X with a total electron dose of about 1800 e-/nm2.

Three Dimensional structure and organization of diploid chromosomes by optical section microscopy

1987 ◽  
Vol 45 ◽  
pp. 633-635
Author(s):  
David A. Agard ◽  
Yasushi Hiraoka ◽  
John W. Sedat
Keyword(s):  
Dimensional Space ◽  
Three Dimensional ◽  
Developmental State ◽  
Mitotic Cell ◽  
Biological Properties ◽  
Dimensional Structure ◽  
Specific Gene ◽  
Three Dimensional Structure ◽  
Complementary Techniques ◽  
Dynamic Structures

In an effort to understand the complex relationship between structure and biological function within the nucleus, we have embarked on a program to examine the three-dimensional structure and organization of Drosophila melanogaster embryonic chromosomes. Our overall goal is to determine how DNA and proteins are organized into complex and highly dynamic structures (chromosomes) and how these chromosomes are arranged in three dimensional space within the cell nucleus. Futher, we hope to be able to correlate structual data with such fundamental biological properties as stage in the mitotic cell cycle, developmental state and transcription at specific gene loci.Towards this end, we have been developing methodologies for the three-dimensional analysis of non-crystalline biological specimens using optical and electron microscopy. We feel that the combination of these two complementary techniques allows an unprecedented look at the structural organization of cellular components ranging in size from 100A to 100 microns.

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