Integrative analysis reveals unique features of the Smc5/6 complex

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 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.


Author(s):  
Changhyun Pang ◽  
Chanseok Lee ◽  
Hoon Eui Jeong ◽  
Kahp-Yang Suh

Close observation of various attachment systems in animal skins has revealed various exquisite multi-scale architectures for essential functions such as locomotion, crawling, mating, and protection from predators. Some of these adhesion systems of geckos and beetles have unique structural features (e.g. high-aspect ratio, tilted angle, and hierarchical nanostructure), resulting in mechanical interlocking mediated by van der Waals forces or liquid secretion (capillary force). In this chapter, we present an overview of recent advances in bio-inspired, artificial dry adhesives, and biomimetics in the context of nanofabrication and material properties. In addition, relevant bio-inspired structural materials, devices (clean transportation device, interlocker, biomedical skin patch, and flexible strain-gauge sensor) and microrobots are briefly introduced, which would shed light on future smart, directional, and reversible adhesion systems.


2021 ◽  
Author(s):  
V. Svistun ◽  
P. Pigulevskiy

Author(s):  
Kai Li ◽  
Yihui Zhao ◽  
Maiqi Liu ◽  
Xiaoying Wang ◽  
Fangyuan Zhang ◽  
...  

Abstract Micro/nano scale structure as important functional part have been widely used in wearable flexible sensors, gas sensors, biological tissue engineering, microfluidic chips super capacitors and so on. Here a multi-scale electrohydrodynamic jet (E-Jet) 3D printing approach regulated by structured multi-physics fields was demonstrated to generate 800 nm scale 2D geometries and high aspect ratio 3D structures. The simulation model of jetting process under resultant effect of top fluid field, middle electric field and bottom thermal field was established. And the physical mechanism and scale law of jet formation were studied. The effects of thermal field temperature, applied voltage and flow rate on the jet behaviors were studied; and the range of process parameters of stable jet was obtained. The regulation of printing parameters was used to manufacture the high resolution gradient graphics and the high aspect ratio structure with tight interlayer bonding. The structural features could be flexibly adjusted by reasonably matching the process parameters. Finally, PCL/PVP composite scaffolds with cell-scale fiber and ordered fiber spacing were printed. The proposed E-Jet printing method provides an alternative approach for the application of biopolymer materials in tissue engineering.


2019 ◽  
Vol 75 (5) ◽  
pp. 1073-1085.e6 ◽  
Author(s):  
Cristina Puchades ◽  
Bojian Ding ◽  
Albert Song ◽  
R. Luke Wiseman ◽  
Gabriel C. Lander ◽  
...  

2014 ◽  
Vol 70 (6) ◽  
pp. 1659-1668 ◽  
Author(s):  
Kwang-Hyun Park ◽  
Jong-Hyun Jung ◽  
Sung-Goo Park ◽  
Myeong-Eun Lee ◽  
James F. Holden ◽  
...  

A novel maltose-forming α-amylase (PSMA) was recently found in the hyperthermophilic archaeonPyrococcussp. ST04. This enzyme shows <13% amino-acid sequence identity to other known α-amylases and displays a unique enzymatic property in that it hydrolyzes both α-1,4-glucosidic and α-1,6-glucosidic linkages of substrates, recognizing only maltose units, in an exo-type manner. Here, the crystal structure of PSMA at a resolution of 1.8 Å is reported, showing a tight ring-shaped tetramer with monomers composed of two domains: an N-domain (amino acids 1–341) with a typical GH57 family (β/α)7-barrel fold and a C-domain (amino acids 342–597) composed of α-helical bundles. A small closed cavity observed in proximity to the catalytic residues Glu153 and Asp253 at the domain interface has the appropriate volume and geometry to bind a maltose unit, accounting for the selective exo-type maltose hydrolysis of the enzyme. A narrow gate at the putative subsite +1 formed by residue Phe218 and Phe452 is essential for specific cleavage of glucosidic bonds. The closed cavity at the active site is connected to a short substrate-binding channel that extends to the central hole of the tetramer, exhibiting a geometry that is significantly different from classical maltogenic amylases or β-amylases. The structural features of this novel exo-type maltose-forming α-amylase provide a molecular basis for its unique enzymatic characteristics and for its potential use in industrial applications and protein engineering.


2019 ◽  
Author(s):  
Cristina Puchades ◽  
Bojian Ding ◽  
Albert Song ◽  
R. Luke Wiseman ◽  
Gabriel C. Lander ◽  
...  

AbstractMitochondrial AAA+ quality control proteases regulate diverse aspects of mitochondrial biology through specialized protein degradation, but the underlying molecular mechanisms that define the diverse activities of these enzymes remain poorly defined. The mitochondrial AAA+ protease AFG3L2 is of particular interest, as genetic mutations localized throughout AFG3L2 are linked to diverse neurodegenerative disorders. However, a lack of structural data has limited our understanding of how mutations impact enzymatic activity. Here, we used cryo-EM to determine a substrate-bound structure of the catalytic core of human AFG3L2. This structure identifies multiple specialized structural features within AFG3L2 that integrate with conserved structural motifs required for hand-over-hand ATP-dependent substrate translocation to engage, unfold and degrade targeted proteins. Mapping disease-relevant AFG3L2 mutations onto our structure demonstrates that many of these mutations localize to these unique structural features of AFG3L2 and distinctly influence its activity and stability. Our results provide a molecular basis for neurological phenotypes associated with different AFG3L2 mutations, and establish a structural framework to understand how different members of the AAA+ superfamily achieve specialized, diverse biological functions.


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.


Sign in / Sign up

Export Citation Format

Share Document