scholarly journals Assembly manual for the proteasome regulatory particle: the first draft

2010 ◽  
Vol 38 (1) ◽  
pp. 6-13 ◽  
Author(s):  
Soyeon Park ◽  
Geng Tian ◽  
Jeroen Roelofs ◽  
Daniel Finley
Keyword(s):  
Biochemical Study ◽  
Release Mechanism ◽  
Substrate Selection ◽  
Core Particle ◽  
Genetic Studies ◽  
Macromolecular Assembly ◽  
Assembly Pathway ◽  
Ongoing Work ◽  
The Common ◽  
Regulatory Particle

The proteasome is the most complex protease known, with a molecular mass of approx. 3 MDa and 33 distinct subunits. Recent studies reported the discovery of four chaperones that promote the assembly of a 19-subunit subcomplex of the proteasome known as the regulatory particle, or RP. These and other findings define a new and highly unusual macromolecular assembly pathway. The RP mediates substrate selection by the proteasome and injects substrates into the CP (core particle) to be degraded. A heterohexameric ring of ATPases, the Rpt proteins, is critical for RP function. These ATPases abut the CP and their C-terminal tails help to stabilize the RP–CP interface. ATPase heterodimers bound to the chaperone proteins are early intermediates in assembly of the ATPase ring. The four chaperones have the common feature of binding the C-domains of Rpt proteins, apparently a remarkable example of convergent evolution; each chaperone binds a specific Rpt subunit. The C-domains are distinct from the C-terminal tails, but are proximal to them. Some, but probably not all, of the RP chaperones appear to compete with CP for binding of the Rpt proteins, as a result of the proximity of the tails to the C-domain. This competition may underlie the release mechanism for these chaperones. Genetic studies in yeast point to the importance of the interaction between the CP and the Rpt tails in assembly, and a recent biochemical study in mammals suggests that RP assembly takes place on pre-assembled CP. These results do not exclude a parallel CP-independent pathway of assembly. Ongoing work should soon clarify the roles of both the CP and the four chaperones in RP assembly.

scholarly journals In-depth Analysis of the Lid Subunits Assembly Mechanism in Mammals

Biomolecules ◽  
2019 ◽  
Vol 9 (6) ◽  
pp. 213 ◽  
Author(s):  
Minghui Bai ◽  
Xian Zhao ◽  
Kazutaka Sahara ◽  
Yuki Ohte ◽  
Yuko Hirano ◽  
...  
Keyword(s):  
26S Proteasome ◽  
Core Particle ◽  
Proteasome Subunit ◽  
Ubiquitinated Proteins ◽  
Assembly Pathway ◽  
Assembly Mechanism ◽  
Depth Analysis ◽  
Regulatory Particle ◽  
Assembly Intermediate ◽  
Assembly Pathways

The 26S proteasome is a key player in the degradation of ubiquitinated proteins, comprising a 20S core particle (CP) and a 19S regulatory particle (RP). The RP is further divided into base and lid subcomplexes, which are assembled independently from each other. We have previously demonstrated the assembly pathway of the CP and the base by observing assembly intermediates resulting from knockdowns of each proteasome subunit and the assembly chaperones. In this study, we examine the assembly pathway of the mammalian lid, which remains to be elucidated. We show that the lid assembly pathway is conserved between humans and yeast. The final step is the incorporation of Rpn12 into the assembly intermediate consisting of two modular complexes, Rpn3-7-15 and Rpn5-6-8-9-11, in both humans and yeast. Furthermore, we dissect the assembly pathways of the two modular complexes by the knockdown of each lid subunit.

scholarly journals The Assembly Pathway of the 19S Regulatory Particle of the Yeast 26S Proteasome

2007 ◽  
Vol 18 (2) ◽  
pp. 569-580 ◽  
Author(s):  
Erika Isono ◽  
Kiyoshi Nishihara ◽  
Yasushi Saeki ◽  
Hideki Yashiroda ◽  
Naoko Kamata ◽  
...  
Keyword(s):  
26S Proteasome ◽  
Restrictive Temperature ◽  
Enzyme Complex ◽  
Core Particle ◽  
Yeast Saccharomyces Cerevisiae ◽  
The Core ◽  
Assembly Pathway ◽  
Regulatory Particle ◽  
Mutant Cells

The 26S proteasome consists of the 20S proteasome (core particle) and the 19S regulatory particle made of the base and lid substructures, and it is mainly localized in the nucleus in yeast. To examine how and where this huge enzyme complex is assembled, we performed biochemical and microscopic characterization of proteasomes produced in two lid mutants, rpn5-1 and rpn7-3, and a base mutant ΔN rpn2, of the yeast Saccharomyces cerevisiae. We found that, although lid formation was abolished in rpn5-1 mutant cells at the restrictive temperature, an apparently intact base was produced and localized in the nucleus. In contrast, in ΔN rpn2 cells, a free lid was formed and localized in the nucleus even at the restrictive temperature. These results indicate that the modules of the 26S proteasome, namely, the core particle, base, and lid, can be formed and imported into the nucleus independently of each other. Based on these observations, we propose a model for the assembly process of the yeast 26S proteasome.

scholarly journals Maturation of the proteasome core particle induces an affinity switch that controls regulatory particle association

2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Prashant S. Wani ◽  
Michael A. Rowland ◽  
Alex Ondracek ◽  
Eric J. Deeds ◽  
Jeroen Roelofs
Keyword(s):  
Core Particle ◽  
Regulatory Particle ◽  
Particle Association

From Silos to Barns? Regional Institutions in International Political Economy

2021 ◽  
Author(s):  
Etel Solingen
Keyword(s):  
Political Economy ◽  
Critical Theory ◽  
Transaction Costs ◽  
Political Science ◽  
Economic Efficiency ◽  
International Political Economy ◽  
Regional Economic ◽  
Regional Institutions ◽  
Ongoing Work ◽  
The Common

The explosion of research on regional economic institutions (REI) over the last two decades has led to a richer understanding of why they emerge, what form they take, and what effects they have. This chapter argues that research on REI is not a monopoly of any particular theoretical, methodological, or epistemological approach. Ongoing work leans not merely on standard political science and economics but on sociology, psychology, and critical theory. Yet, REI studies cluster in silos more often than barns, although this chapter highlights some research programs with potential for fostering barns. Exclusive attention to power, economic efficiency, transaction costs, and transnational normative diffusion—the common analytical currency in standard accounts of REI—may conceal deeper domestic drivers underlying REI dynamics.

scholarly journals Comparative Analysis of In Vitro Responses and Regeneration between Diverse Bioenergy Sorghum Genotypes

Plants ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 248
Author(s):  
Barry Flinn ◽  
Savanah Dale ◽  
Andrew Disharoon ◽  
Stephen Kresovich
Keyword(s):  
Plantlet Regeneration ◽  
Induction Phase ◽  
Genetic Studies ◽  
Response Profiles ◽  
The Common ◽  
Parental Lines ◽  
Sorghum Genotypes ◽  
Better Than

Sorghum has been considered a recalcitrant plant in vitro and suffers from a lack of regeneration protocols that function broadly and efficiently across a range of genotypes. This study was initiated to identify differential genotype-in vitro protocol responses across a range of bioenergy sorghum parental lines and the common grain sorghum genotype Tx430 in order to characterize response profiles for use in future genetic studies. Two different in vitro protocols, LG and WU, were used for comparisons. Distinct genotype-protocol responses were observed, and the WU protocol performed significantly better for plantlet regeneration. Most bioenergy genotypes performed as well, if not better than Tx430, with Rio and PI329311 as the top regenerating lines. Genotypes displayed protocol-dependent, differential phenolic exudation responses, as indicated by medium browning. During the callus induction phase, genotypes prone to medium browning exhibited a response on WU medium which was either equal or greater than on LG medium. Genotype- and protocol-dependent albino plantlet regeneration was also noted, with three of the bioenergy genotypes showing albino plantlet regeneration. Grassl, Rio and Pink Kafir were susceptible to albino plantlet regeneration, with the response strongly associated with the WU protocol. These bioenergy parental genotypes, and their differential responses under two in vitro protocols, provide tools to further explore and assess the role of genetic loci, candidate genes, and allelic variants in the regulation of in vitro responsiveness in sorghum.

scholarly journals Ubiquitinated proteins promote the association of proteasomes with the deubiquitinating enzyme Usp14 and the ubiquitin ligase Ube3c

2017 ◽  
Vol 114 (17) ◽  
pp. E3404-E3413 ◽  
Author(s):  
Chueh-Ling Kuo ◽  
Alfred Lewis Goldberg
Keyword(s):  
Ubiquitin Ligase ◽  
Mammalian Cells ◽  
Proteasome Activity ◽  
Deubiquitinating Enzyme ◽  
Core Particle ◽  
Ubiquitinated Proteins ◽  
Protein Ubiquitination ◽  
Cell Extracts ◽  
Regulatory Particle ◽  
In Cells

In mammalian cells, the 26S proteasomes vary in composition. In addition to the standard 28 subunits in the 20S core particle and 19 subunits in each 19S regulatory particle, a small fraction (about 10–20% in our preparations) also contains the deubiquitinating enzyme Usp14/Ubp6, which regulates proteasome activity, and the ubiquitin ligase, Ube3c/Hul5, which enhances proteasomal processivity. When degradation of ubiquitinated proteins in cells was inhibited, levels of Usp14 and Ube3c on proteasomes increased within minutes. Conversely, when protein ubiquitination was prevented, or when purified proteasomes hydrolyzed the associated ubiquitin conjugates, Usp14 and Ube3c dissociated rapidly (unlike other 26S subunits), but the inhibitor ubiquitin aldehyde slowed their dissociation. Recombinant Usp14 associated with purified proteasomes preferentially if they contained ubiquitin conjugates. In cells or extracts, adding Usp14 inhibitors (IU-1 or ubiquitin aldehyde) enhanced Usp14 and Ube3c binding further. Thus, in the substrate- or the inhibitor-bound conformations, Usp14 showed higher affinity for proteasomes and surprisingly enhanced Ube3c binding. Moreover, adding ubiquitinated proteins to cell extracts stimulated proteasome binding of both enzymes. Thus, Usp14 and Ube3c cycle together on and off proteasomes, and the presence of ubiquitinated substrates promotes their association. This mechanism enables proteasome activity to adapt to the supply of substrates.

Rheumatological manifestations of endocrine disorders

2013 ◽  
Author(s):  
Sanjeev Sharma ◽  
Gerry Rayman
Keyword(s):  
Population Studies ◽  
Endocrine Disorders ◽  
Genetic Studies ◽  
Comprehensive List ◽  
Clinical Presentations ◽  
Organ Systems ◽  
Musculoskeletal Manifestations ◽  
The Common ◽  
Clinical Conditions ◽  
Rheumatological Manifestations

There is considerable overlap of musculoskeletal manifestations of both rheumatological and endocrine disorders. Apart for the well-described autoimmune basis governing the aetiopathogenesis of clinical states pertaining to specific conditions affecting both systems, there is more recent evidence on the overlapping biology and genetics of these organ systems. Not uncommonly, endocrine manifestations can herald the initial presentation of rheumatological illnesses and the converse holds true for endocrinopathies. Rheumatologists and physicians alike need to be astutely aware of this overlap of symptomatology and also the physiology linking both groups of clinical conditions. This review discusses the common endocrine presentations associated with rheumatic illnesses in relation to newer information gleaned from population studies, genetic studies, and clinical presentations. A comprehensive list of rheumatological conditions found in endocrine states is also tabulated at the end.

Dihaploid induction ability of three clones of Solanum phureja (2n = 2x = 24) in interploidy cross with S. tuberosum (2n = 4x = 48)

2010 ◽  
Vol 58 (1) ◽  
pp. 49-54
Author(s):  
J. Panahandeh
Keyword(s):  
Male Fertility ◽  
Marker Gene ◽  
Seed Parent ◽  
Genetic Studies ◽  
Interploidy Crosses ◽  
Tuber Colour ◽  
The Common ◽  
Tetraploid Level ◽  
Pollen Shed ◽  
The Given

Potato, Solanum tuberosum L. (2n = 4x = 48), is an autotetraploid species, the breeding of which at the tetraploid level is complicated by tetrasomic inheritance. Dihaploids (2n = 2x = 24) from the tetraploid cultivated potato have great potential for breeding and genetic studies. The common method deployed to obtain potato dihaploids is to make interspecific-interploidy (4x × 2x) crosses between a tetraploid seed parent and special clones from the diploid S. phureja as pollinator. Pollinators carrying a marker gene have been used, but unfortunately, these clones were very weak, with rare flowering and low male fertility under the given conditions. To find a suitable pollinator, three clones were selected from S. phureja based on flowering, pollen shed and male fertility and were crossed with five cultivated tetraploid potatoes to evaluate their dihaploid induction ability. A total of 1529 interploidy crosses were made, resulting in 1116 berries and 1456 seeds. The progeny were divided into two groups based on stem, flower and tuber colour: hybrids and non-hybrids (putative dihaploids). Chromosome counting in non-hybrid genotypes detected 39 dihaploids. The clone phu 3 and cv. Picasso, with 12.1 and 10.7 dihaploids per 100 berries, respectively, were the best dihaploid inducer and seed parent for dihaploid production.

A Biomechanical Approach to Alpine Ski Binding Design

1989 ◽  
Vol 5 (3) ◽  
pp. 308-323 ◽  
Author(s):  
Glenn S. Wunderly ◽  
Maury L. Hull
Keyword(s):  
Laboratory Tests ◽  
Release Mechanism ◽  
Tibial Shaft ◽  
New Approach ◽  
Forward Bending ◽  
Frictional Forces ◽  
The Common ◽  
Quasistatic Loading ◽  
Release Consistency ◽  
Biomechanical Approach

A new approach to ski binding design is advanced. It begins with a release locus derived from injury mechanics research and knowledge of the expected loading conditions and then incorporates these into the final binding design. A mechanical ski binding designed by following the new approach is presented. This binding offers a number of performance features not found in commercially available designs. One feature is the ability to eliminate the axial force supported by the tibial shaft from affecting release in forward bending. A second feature is the binding’s ability to release according to virtually any preprogrammed locus of the combination of moments in both bending and torsion. A third feature is a release mechanism that is insensitive to the common frictional forces that affect the release consistency of conventional heel/toe bindings. In addition to these features, the binding offers a variety of operational conveniences. The presentation of the binding not only describes the design details but also evaluates the release performance (i.e., locus and consistency) based upon laboratory tests under quasistatic loading.

scholarly journals The Plot Thickens: Haploid and Triploid-Like Thalli, Hybridization, and Biased Mating Type Ratios in Letharia

2021 ◽  
Vol 2 ◽  
Author(s):  
Sandra Lorena Ament-Velásquez ◽  
Veera Tuovinen ◽  
Linnea Bergström ◽  
Toby Spribille ◽  
Dan Vanderpool ◽  
...  
Keyword(s):  
Mating Type ◽  
Pure Culture ◽  
Natural Populations ◽  
Common Belief ◽  
Genetic Studies ◽  
Type Locus ◽  
Genomic Study ◽  
The Common ◽  
Mat Locus

The study of the reproductive biology of lichen fungal symbionts has been traditionally challenging due to their complex lifestyles. Against the common belief of haploidy, a recent genomic study found a triploid-like signal in Letharia. Here, we infer the genome organization and reproduction in Letharia by analyzing genomic data from a pure culture and from thalli, and performing a PCR survey of the MAT locus in natural populations. We found that the read count variation in the four Letharia specimens, including the pure culture derived from a single sexual spore of L. lupina, is consistent with haploidy. By contrast, the L. lupina read counts from a thallus' metagenome are triploid-like. Characterization of the mating-type locus revealed a conserved heterothallic configuration across the genus, along with auxiliary genes that we identified. We found that the mating-type distributions are balanced in North America for L. vulpina and L. lupina, suggesting widespread sexual reproduction, but highly skewed in Europe for L. vulpina, consistent with predominant asexuality. Taken together, we propose that Letharia fungi are heterothallic and typically haploid, and provide evidence that triploid-like individuals are hybrids between L. lupina and an unknown Letharia lineage, reconciling classic systematic and genetic studies with recent genomic observations.

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