scholarly journals Integrative analysis reveals unique structural and functional features of the Smc5/6 complex

2021 ◽  
Vol 118 (19) ◽  
pp. e2026844118
Author(s):  
You Yu ◽  
Shibai Li ◽  
Zheng Ser ◽  
Tanmoy Sanyal ◽  
Koyi Choi ◽  
...  

Structural maintenance of chromosomes (SMC) complexes are critical chromatin modulators. In eukaryotes, the cohesin and condensin SMC complexes organize chromatin, while the Smc5/6 complex directly regulates DNA replication and repair. The molecular basis for the distinct functions of Smc5/6 is poorly understood. Here, we report an integrative structural study of the budding yeast Smc5/6 holo-complex using electron microscopy, cross-linking mass spectrometry, and computational modeling. We show that the Smc5/6 complex possesses several unique features, while sharing some architectural characteristics with other SMC complexes. In contrast to arm-folded structures of cohesin and condensin, Smc5 and Smc6 arm regions do not fold back on themselves. Instead, these long filamentous regions interact with subunits uniquely acquired by the Smc5/6 complex, namely the Nse2 SUMO ligase and the Nse5/Nse6 subcomplex, with the latter also serving as a linchpin connecting distal parts of the complex. Our 3.0-Å resolution cryoelectron microscopy structure of the Nse5/Nse6 core further reveals a clasped-hand topology and a dimeric interface important for cell growth. Finally, we provide evidence that Nse5/Nse6 uses its SUMO-binding motifs to contribute to Nse2-mediated sumoylation. Collectively, our integrative study identifies distinct structural features of the Smc5/6 complex and functional cooperation among its coevolved unique subunits.

2021 ◽  
Author(s):  
You Yu ◽  
Shibai Li ◽  
Zheng Ser ◽  
Tanmoy Sanyal ◽  
Koyi Choi ◽  
...  

AbstractStructural maintenance of chromosomes (SMC) complexes are critical chromatin modulators. In eukaryotes, the cohesin and condensin SMC complexes organize chromatin, while the Smc5/6 complex directly regulates DNA replication and repair. The molecular basis for Smc5/6’s distinct functions is currently poorly understood. Here, we report an integrative structural study of the budding yeast Smc5/6 complex using electron microscopy, cross-linking mass spectrometry, and computational modeling. We show that while the complex shares a similar overall organization with other SMC complexes, it possesses several unique features. In contrast to the reported folded-arm structures of cohesin and condensin, our data suggest that Smc5 and Smc6 arm regions do not fold back on themselves. Instead, these long filamentous regions interact with subunits uniquely acquired by the Smc5/6 complex, namely the Nse2 SUMO ligase and the Nse5-Nse6 subcomplex. Further, we show that Nse5-Nse6 subcomplex adopts a novel structure with an extensive dimerization interface and multiple domains contacting other subunits of the Smc5/6 complex. We also provide evidence that the Nse5-Nse6 module uses its SUMO-binding motifs to contribute to Nse2-mediated sumoylation. Collectively, our integrative multi-scale study identifies distinct structural features of the Smc5/6 complex and functional cooperation amongst its co-evolved unique subunits.


2021 ◽  
Vol 12 (1) ◽  
pp. 96-102
Author(s):  
E. A. Flerova

At present, special attention is drawn to the study of the adaptation of aquatic organisms to a complex of environmental factors precisely at the cellular level. It is very important to study the structural and functional features of the kidney, which not only plays a key role in osmoregulation, but also makes a significant contribution to maintaining homeostasis at the level of functioning of a single nonspecific defense system of the body. In this aspect, the study of species belonging to a unique ancient group, united in the order salmoniformes, is highly relevant. Using the methods of light and electron microscopy, we investigated the morphology and ultrastructure of the mesonephros of the population of the semianadromous ecological form European smelt Osmerus eperlanus inhabiting the Gulf of Finland of the Baltic Sea and performing spawning migrations in the Luga River of the Leningrad Region. The general scheme of the trunk kidney organization is given, the structural features and the ratio of leukocytes and structures of the smelt nephron are revealed. It is shown that the development of hematopoietic tissue in the mesonephros, the number of mature forms of granulocytes are systematic signs which do not depend on the ecology of the species. The ratio of leukocytes, the width of the cisterns of the rough endoplasmic reticulum of plasma cells, the structure and number of granules in granulocytes are associated with the peculiarities of the functioning of the cellular link of the immune system under certain conditions of the species habitat. The ultrafine structure of the ion-transporting interstitial cells, as well as the ultrastructural features found in the smelt nephron, can be considered cytological markers of smelt adaptation to a semianadromous lifestyle.


2017 ◽  
Author(s):  
Daniel I. Chu ◽  
Margaret M Romine

The colon, appendix, rectum, and anus have unique anatomic features, both structural and functional, that contribute to normal and pathologic states. Structural features discussed in this review include the layers of the intestinal wall, vascular anatomy, lymphatic drainage, and innervation. Functional features highlighted include the role(s) each organ plays in immunity, nutrient absorption, electrolyte secretion, water absorption, continence, and elimination of waste. A clear understanding of these structural and functional details is the foundation on which surgical techniques and treatment strategies are based when addressing surgical pathology. Key words: anus, appendix, colon, colorectal pathology, colorectal surgery, rectum


Author(s):  
Valentyna Bebykh ◽  
Natalia Bytsko

The article deals with the dynamic and evolutionary processes of eponymous terms formation in medicine in the systems of English and Ukrainian languages. The aim of the work is to systematize medical propriatives on the basis of such defining features as denotative-characteristic, etymological-word-forming and functional features. Methods and techniques adopted in onomastics and stylistics were used, such as: textual and stylistic analysis, classification of onomastic material, structural, etymological and word-formation analysis, analysis of variants of names, synthesis and identification of patterns. The research focuses on lexical and semantic features and structural features of medical terms with an onymic component. The scientific research of domestic and foreign researchers on the presence or absence of a clear boundary between common and proper names is analyzed. The ways of origin of propriatives and ways of forming a layer of onymic medical vocabulary are outlined. Based on the samples of eponymous terms in accordance with the fields of medicine, in particular rheumatology and neurology, anatomy and clinical nomenclature, the characteristics of dynamic and evolutionary processes in each of the subsystems is presented: quantitative ratio data are given, ways and methods of formation are identified, the role and place of eponyms in medical phenomena and objects are determined, the structural features of these terminological units are described. Much attention is paid to the process of transforming proper names into common words. The processes of transition of proper names into common names, which occur in medical terminology, differences of propriatives and appellates in functions, properties, mechanism of development, essence and linguistic features, context, etymology and translation are studied.


Author(s):  
D.R. Kasimov

The article provides a new classification of evaluative concepts enshrined in the Criminal Code of the Russian Federation, indicates the purpose of its existence in the doctrine of criminal law. The article describes the definition of constitutive evaluative concepts that are determined as legislatively vague evaluative concepts that, by their normative-essential and functionally-substantive characteristics, are absolute, necessarily alternative, or accompanying structural features of a crime. Through the prism of the features of constitutive evaluative concepts, their varieties, essential features and functions are distinguished; interpretation (including cognitive) meaning is revealed. Moreover, the interpretation features of these evaluative concepts are considered in two interdependent aspects: the structurally-essential (associated with the types, attributes and functions of constitutive evaluative concepts) and the procedural-substantive (associated with the informative and informative activities of the interpreter). It is indicated that the interpretation features of an structurally-essential nature are, firstly, in the composition and criminogenic properties of constitutive evaluative concepts, and secondly, in the semantic structural composition, indicating a meaningful dependence of the evaluative concept on the accompanying structural features of a crime, and thirdly, legally significant functional features. At the same time, interpretative features of a procedural-substantive order are also highlighted, which include, firstly, the need for a paramount definition of the criminogenic determinant, designed to establish the structural features of a crime in a perfect act, and secondly, in an increased degree of normative casuistic derivative of these evaluative concepts. The author comes to the conclusion that constitutive evaluative concepts are interpreted according to the same logical-linguistic and legal laws, but with some marked structurally meaningful features.


PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e3389 ◽  
Author(s):  
Yosvany López ◽  
Alexis Vandenbon ◽  
Akinao Nose ◽  
Kenta Nakai

Because transcription is the first step in the regulation of gene expression, understanding how transcription factors bind to their DNA binding motifs has become absolutely necessary. It has been shown that the promoters of genes with similar expression profiles share common structural patterns. This paper presents an extensive study of the regulatory regions of genes expressed in 24 developmental stages ofDrosophila melanogaster. It proposes the use of a combination of structural features, such as positioning of individual motifs relative to the transcription start site, orientation, pairwise distance between motifs, and presence of motifs anywhere in the promoter for predicting gene expression from structural features of promoter sequences. RNA-sequencing data was utilized to create and validate the 24 models. When genes with high-scoring promoters were compared to those identified by RNA-seq samples, 19 (79.2%) statistically significant models, a number that exceeds previous studies, were obtained. Each model yielded a set of highly informative features, which were used to search for genes with similar biological functions.


2017 ◽  
Author(s):  
Daniel I. Chu ◽  
Margaret M Romine

The colon, appendix, rectum, and anus have unique anatomic features, both structural and functional, that contribute to normal and pathologic states. Structural features discussed in this review include the layers of the intestinal wall, vascular anatomy, lymphatic drainage, and innervation. Functional features highlighted include the role(s) each organ plays in immunity, nutrient absorption, electrolyte secretion, water absorption, continence, and elimination of waste. A clear understanding of these structural and functional details is the foundation on which surgical techniques and treatment strategies are based when addressing surgical pathology. This review contains 7 highly rendered figures, 3 tables, and 58 references. Key words: anus, appendix, colon, colorectal pathology, colorectal surgery, rectum


2011 ◽  
Vol 435 (2) ◽  
pp. 411-420 ◽  
Author(s):  
Efthalia Zervoudi ◽  
Athanasios Papakyriakou ◽  
Dimitra Georgiadou ◽  
Irini Evnouchidou ◽  
Anna Gajda ◽  
...  

ERAP1 (endoplasmic reticulum aminopeptidase 1), ERAP2 and IRAP (insulin-regulated aminopeptidase) are three homologous enzymes that play critical roles in the generation of antigenic peptides. These aminopeptidases excise amino acids from N-terminally extended precursors of antigenic peptides in order to generate the correct length epitopes for binding on to MHC class I molecules. The specificity of these peptidases can affect antigenic peptide selection, but has not yet been investigated in detail. In the present study we utilized a collection of 82 fluorigenic substrates to define a detailed selectivity profile for each of the three enzymes and to probe structural and functional features of the S1 (primary specificity) pocket. Molecular modelling of the three S1 pockets reveals substrate–enzyme interactions that are critical determinants for specificity. The substrate selectivity profiles suggest that IRAP largely combines the S1 specificity of ERAP1 and ERAP2, consistent with its proposed biological function. IRAP, however, does not achieve this dual specificity by simply combining structural features of ERAP1 and ERAP2, but rather by an unique amino acid change at position 541. The results of the present study provide insights on antigenic peptide selection and may prove valuable in designing selective inhibitors or activity markers for this class of enzymes.


2017 ◽  
Author(s):  
Anna Letizia Allegra Mascaro ◽  
Emilia Conti ◽  
Stefano Lai ◽  
Antonino Paolo Di Giovanna ◽  
Cristina Spalletti ◽  
...  

AbstractRehabilitation is the most effective treatment for promoting the recovery of motor deficits after stroke. Despite its importance, the processes associated with rehabilitative intervention are poorly understood. One of the most challenging experimental goals is to unambiguously link specific circuit changes induced by rehabilitation to improved behavior. Here, we investigate which facets of cortical remodeling are induced by rehabilitation by combining optical imaging and manipulation tools in a mouse model of stroke. We demonstrate the progressive restoration of cortical motor maps and of cortical activity in parallel with the reinforcement of inter-hemispheric connectivity after rehabilitation. Furthermore, we reveal that the increase in vascular density goes along with the stabilization of peri-infarct neural circuitry at synaptic level. The present work provides the first evidences that rehabilitation is sufficient to promote the combined recovery of distinct structural and functional features distinctive of healthy neuronal networks.


2020 ◽  
Vol 48 (5) ◽  
pp. 2159-2171 ◽  
Author(s):  
Roger Solé-Soler ◽  
Jordi Torres-Rosell

The Smc5/6 complex plays essential roles in chromosome segregation and repair, by promoting disjunction of sister chromatids. The core of the complex is constituted by an heterodimer of Structural Maintenance of Chromosomes (SMC) proteins that use ATP hydrolysis to dynamically associate with and organize chromosomes. In addition, the Smc5/6 complex contains six non-SMC subunits. Remarkably, and differently to other SMC complexes, the Nse1 and Nse2 subunits contain RING-type domains typically found in E3 ligases, pointing to the capacity to regulate other proteins and complexes through ubiquitin-like modifiers. Nse2 codes for a C-terminal SP-RING domain with SUMO ligase activity, assisting Smc5/6 functions in chromosome segregation through sumoylation of several chromosome-associated proteins. Nse1 codes for a C-terminal NH-RING domain and, although it has been proposed to have ubiquitin ligase activity, no Smc5/6-dependent ubiquitylation target has been described to date. Here, we review the function of the two RING domains of the Smc5/6 complex in the broader context of SMC complexes as global chromosome organizers of the genome.


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