scholarly journals Higher-order structure of the 30-nm chromatin fiber revealed by cryo-EM

IUBMB Life ◽  
2016 ◽  
Vol 68 (11) ◽  
pp. 873-878 ◽  
Author(s):  
Ping Zhu ◽  
Guohong Li
Keyword(s):  
Higher Order ◽  
Chromatin Fiber ◽  
Order Structure

scholarly journals Higher order structure in a short repeat length chromatin.

1984 ◽  
Vol 98 (4) ◽  
pp. 1320-1327 ◽  
Author(s):  
J Allan ◽  
D C Rau ◽  
N Harborne ◽  
H Gould
Keyword(s):  
Higher Order ◽  
Chromatin Fiber ◽  
Repeat Length ◽  
Order Structure ◽  
Dependent Manner ◽  
Chicken Erythrocyte ◽  
Base Pairs ◽  
Short Repeat ◽  
Cortical Neurone

Polynucleosomes from calf brain cortical neurone nuclei have an average repeat length of less than 168 base pairs. The ability of this material to adopt higher order structure has been assessed by various physical techniques. Although containing on average less DNA per nucleosome than is required to form a chromatosome, this short repeat length chromatin folded in an H1 dependent manner to a structure with properties similar to those observed for longer repeat length chromatins such as that of chicken erythrocyte (McGhee, J.D., D.C. Rau, E. Charney, and G. Felsenfeld, 1980, Cell, 22:87-96). These observations are discussed in the context of H1 location in the higher order chromatin fiber.

Transitions between in situ and isolated chromatin

1993 ◽  
Vol 105 (2) ◽  
pp. 551-561 ◽  
Author(s):  
P.J. Giannasca ◽  
R.A. Horowitz ◽  
C.L. Woodcock
Keyword(s):  
Higher Order ◽  
Chromatin Fiber ◽  
Sperm Chromatin ◽  
Order Structure ◽  
Native State ◽  
Chromatin Fibers

We show that the mechanism by which chromatin displaying higher-order structure is usually isolated from nuclei involves a transition to an extended nucleosomal arrangement. After being released from nuclei, chromatin must refold in order to produce the typical chromatin fibers observed in solution. For starfish sperm chromatin with a long nucleosome repeat (222 bp), isolated fibers are significantly wider than those in the nucleus, indicating that the refolding process does not regenerate the native higher-order structure. We also propose that for typical eukaryotic nuclei, the concept that the native state of the (inactive) bulk of the genome is a chromatin fiber with defined architecture be reconsidered.

Macrocycles of Higher Ortho-Phenylenes: Assembly and Folding

2019 ◽  
Author(s):  
Zacharias Kinney ◽  
Viraj Kirinda ◽  
Scott Hartley
Keyword(s):  
Chemical Shift ◽  
Higher Order ◽  
Order Structure ◽  
Complex Geometries ◽  
Spatial Relationships ◽  
Predominant Species ◽  
Bite Angle ◽  
Direct Assembly

<p>Higher-order structure in abiotic foldamer systems represents an important but largely unrealized goal. As one approach to this challenge, covalent assembly can be used to assemble macrocycles with foldamer subunits in well-defined spatial relationships. Such systems have previously been shown to exhibit self-sorting, new folding motifs, and dynamic stereoisomerism, yet there remain important questions about the interplay between folding and macrocyclization and the effect of structural confinement on folding behavior. Here, we explore the dynamic covalent assembly of extended <i>ortho</i>-phenylenes (hexamer and decamer) with rod-shaped linkers. Characteristic <sup>1</sup>H chemical shift differences between cyclic and acyclic systems can be compared with computational conformer libraries to determine the folding states of the macrocycles. We show that the bite angle provides a measure of the fit of an <i>o</i>-phenylene conformer within a shape-persistent macrocycle, affecting both assembly and ultimate folding behavior. For the <i>o</i>-phenylene hexamer, the bite angle and conformer stability work synergistically to direct assembly toward triangular [3+3] macrocycles of well-folded oligomers. For the decamer, the energetic accessibility of conformers with small bite angles allows [2+2] macrocycles to be formed as the predominant species. In these systems, the <i>o</i>-phenylenes are forced into unusual folding states, preferentially adopting a backbone geometry with distinct helical blocks of opposite handedness. The results show that simple geometric restrictions can be used to direct foldamers toward increasingly complex geometries.</p>

Macrocycles of Higher ortho-Phenylenes: Assembly and Folding

2019 ◽  
Author(s):  
Zacharias Kinney ◽  
Viraj Kirinda ◽  
Scott Hartley
Keyword(s):  
Chemical Shift ◽  
Higher Order ◽  
Order Structure ◽  
Complex Geometries ◽  
Spatial Relationships ◽  
Predominant Species ◽  
Bite Angle ◽  
Direct Assembly

<p>Higher-order structure in abiotic foldamer systems represents an important but largely unrealized goal. As one approach to this challenge, covalent assembly can be used to assemble macrocycles with foldamer subunits in well-defined spatial relationships. Such systems have previously been shown to exhibit self-sorting, new folding motifs, and dynamic stereoisomerism, yet there remain important questions about the interplay between folding and macrocyclization and the effect of structural confinement on folding behavior. Here, we explore the dynamic covalent assembly of extended <i>ortho</i>-phenylenes (hexamer and decamer) with rod-shaped linkers. Characteristic <sup>1</sup>H chemical shift differences between cyclic and acyclic systems can be compared with computational conformer libraries to determine the folding states of the macrocycles. We show that the bite angle provides a measure of the fit of an <i>o</i>-phenylene conformer within a shape-persistent macrocycle, affecting both assembly and ultimate folding behavior. For the <i>o</i>-phenylene hexamer, the bite angle and conformer stability work synergistically to direct assembly toward triangular [3+3] macrocycles of well-folded oligomers. For the decamer, the energetic accessibility of conformers with small bite angles allows [2+2] macrocycles to be formed as the predominant species. In these systems, the <i>o</i>-phenylenes are forced into unusual folding states, preferentially adopting a backbone geometry with distinct helical blocks of opposite handedness. The results show that simple geometric restrictions can be used to direct foldamers toward increasingly complex geometries.</p>

Current Trends in Biotherapeutic Higher Order Structure Characterization by Irreversible Covalent Footprinting Mass Spectrometry

2019 ◽  
Vol 26 (1) ◽  
pp. 35-43 ◽  
Author(s):  
Natalie K. Garcia ◽  
Galahad Deperalta ◽  
Aaron T. Wecksler
Keyword(s):  
Mass Spectrometry ◽  
Protein Structure ◽  
Protein Interactions ◽  
Quaternary Structure ◽  
Solvent Accessibility ◽  
Higher Order ◽  
Structure Characterization ◽  
Order Structure ◽  
Protein Footprinting ◽  
Wide Range

Background: Biotherapeutics, particularly monoclonal antibodies (mAbs), are a maturing class of drugs capable of treating a wide range of diseases. Therapeutic function and solutionstability are linked to the proper three-dimensional organization of the primary sequence into Higher Order Structure (HOS) as well as the timescales of protein motions (dynamics). Methods that directly monitor protein HOS and dynamics are important for mapping therapeutically relevant protein-protein interactions and assessing properly folded structures. Irreversible covalent protein footprinting Mass Spectrometry (MS) tools, such as site-specific amino acid labeling and hydroxyl radical footprinting are analytical techniques capable of monitoring the side chain solvent accessibility influenced by tertiary and quaternary structure. Here we discuss the methodology, examples of biotherapeutic applications, and the future directions of irreversible covalent protein footprinting MS in biotherapeutic research and development. Conclusion: Bottom-up mass spectrometry using irreversible labeling techniques provide valuable information for characterizing solution-phase protein structure. Examples range from epitope mapping and protein-ligand interactions, to probing challenging structures of membrane proteins. By paring these techniques with hydrogen-deuterium exchange, spectroscopic analysis, or static-phase structural data such as crystallography or electron microscopy, a comprehensive understanding of protein structure can be obtained.

Transdiagnostic dimensions in obsessive-compulsive and related disorders: associations with internalizing and externalizing symptoms

2020 ◽  
pp. 1-9
Author(s):  
Ivar Snorrason ◽  
Courtney Beard ◽  
Andrew D. Peckham ◽  
Thröstur Björgvinsson
Keyword(s):  
Internalizing Symptoms ◽  
Externalizing Symptoms ◽  
Higher Order ◽  
Order Structure ◽  
Obsessive Compulsive ◽  
Addictive Disorders ◽  
Compulsive Disorder ◽  
Alcohol Cravings ◽  
Internalizing And Externalizing ◽  
Internalizing And Externalizing Symptoms

Abstract Background Hierarchical structural models of psychopathology rarely extend to obsessive-compulsive spectrum disorders. The current study sought to examine the higher-order structure of the obsessive-compulsive and related disorders (OCRDs) in DSM-5: obsessive-compulsive disorder (OCD), hoarding disorder (HD), body dysmorphic disorder (BDD), trichotillomania (hair-pulling disorder; HPD) and excoriation (skin-picking) disorder (SPD). Methods Adult patients in a partial hospital program (N = 532) completed a dimensional measure of the five OCRDs. We used confirmatory factor analysis to identify the optimal model of the comorbidity structure. We then examined the associations between the transdiagnostic factors and internalizing and externalizing symptoms (i.e. depression, generalized anxiety, neuroticism, and drug/alcohol cravings). Results The best fitting model included two correlated higher-order factors: an obsessions-compulsions (OC) factor (OCD, BDD, and HD), and a body-focused repetitive behavior (BFRB) factor (HPD and SPD). The OC factor, not the BFRB factor, had unique associations with internalizing symptoms (standardized effects = 0.42–0.66) and the BFRB factor, not the OC factor, had small marginally significant unique association with drug/alcohol cravings (standardized effect = 0.22, p = 0.088). Conclusions The results mirror findings from twin research and indicate that OCD, BDD, and HD share liability that is significantly associated with internalizing symptoms, but this liability may be relatively less important for BFRBs. Further research is needed to better examine the associations between BFRBs and addictive disorders.

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