scholarly journals Differential Complex Formation via Paralogs in the Human Sin3 Protein Interaction Network

2020 ◽  
Vol 19 (9) ◽  
pp. 1468-1484
Author(s):  
Mark K. Adams ◽  
Charles A. S. Banks ◽  
Janet L. Thornton ◽  
Cassandra G. Kempf ◽  
Ying Zhang ◽  
...  
Keyword(s):  
Protein Complexes ◽  
Hdac Inhibitors ◽  
Interaction Network ◽  
Complex Composition ◽  
Binding Partners ◽  
Heterogeneous Nature ◽  
Differential Complex ◽  
The Many ◽  
Target Effects

Despite the continued analysis of HDAC inhibitors in clinical trials, the heterogeneous nature of the protein complexes they target limits our understanding of the beneficial and off-target effects associated with their application. Among the many HDAC protein complexes found within the cell, Sin3 complexes are conserved from yeast to humans and likely play important roles as regulators of transcriptional activity. The presence of two Sin3 paralogs in humans, SIN3A and SIN3B, may result in a heterogeneous population of Sin3 complexes and contributes to our poor understanding of the functional attributes of these complexes. Here, we profile the interaction networks of SIN3A and SIN3B to gain insight into complex composition and organization. In accordance with existing data, we show that Sin3 paralog identity influences complex composition. Additionally, chemical cross-linking MS identifies domains that mediate interactions between Sin3 proteins and binding partners. The characterization of rare SIN3B proteoforms provides additional evidence for the existence of conserved and divergent elements within human Sin3 proteins. Together, these findings shed light on both the shared and divergent properties of human Sin3 proteins and highlight the heterogeneous nature of the complexes they organize.

scholarly journals Differential complex formation via paralogs in the human Sin3 protein interaction network

2019 ◽  
Author(s):  
Mark K. Adams ◽  
Charles A.S. Banks ◽  
Janet L. Thornton ◽  
Mihaela E. Sardiu ◽  
Maxime Killer ◽  
...  
Keyword(s):  
Protein Complexes ◽  
Interaction Network ◽  
Scaffolding Proteins ◽  
Heterogeneous Nature ◽  
Differential Complex ◽  
The Many ◽  
Definition Of ◽  
Sin3 Complex ◽  
Insight Into ◽  
Target Effects

ABSTRACTDespite the continued analysis of HDAC inhibitor efficacy in clinical trials, the heterogeneous nature of the protein complexes they target limits our understanding of the beneficial and off-target effects associated with their application. Among the many HDAC protein complexes found within the cell, Sin3 complexes are conserved from yeast to humans and likely play important roles as regulators of transcriptional activity. The functional attributes of these protein complexes remain poorly characterized in humans. Contributing to the poor definition of Sin3 complex attributes in higher eukaryotes is the presence of two Sin3 scaffolding proteins, SIN3A and SIN3B. Here we show that paralog switching influences the interaction networks of the Sin3 complexes. While SIN3A and SIN3B do have unique interaction network components, we find that SIN3A and SIN3B interact with a common set of proteins. Additionally, our results suggest that SIN3A and SIN3B may possess the capacity to form hetero-oligomeric complexes. While one principal form of SIN3B exists in humans, the analysis of rare SIN3B proteoforms provides insight into the domain organization of SIN3B. Together, these findings shed light on the shared and divergent properties of human Sin3 proteins and highlight the heterogeneous nature of the complexes they organize.

scholarly journals Relative interfacial cleavage energetics of protein complexes revealed by surface collisions

2019 ◽  
Vol 116 (17) ◽  
pp. 8143-8148 ◽  
Author(s):  
Sophie R. Harvey ◽  
Justin T. Seffernick ◽  
Royston S. Quintyn ◽  
Yang Song ◽  
Yue Ju ◽  
...  
Keyword(s):  
Computational Models ◽  
Protein Complexes ◽  
Specific Binding ◽  
Native Mass Spectrometry ◽  
Binding Affinities ◽  
Training Set ◽  
Subunit Interactions ◽  
Binding Partners ◽  
Relative Binding

To fulfill their biological functions, proteins must interact with their specific binding partners and often function as large assemblies composed of multiple proteins or proteins plus other biomolecules. Structural characterization of these complexes, including identification of all binding partners, their relative binding affinities, and complex topology, is integral for understanding function. Understanding how proteins assemble and how subunits in a complex interact is a cornerstone of structural biology. Here we report a native mass spectrometry (MS)-based method to characterize subunit interactions in globular protein complexes. We demonstrate that dissociation of protein complexes by surface collisions, at the lower end of the typical surface-induced dissociation (SID) collision energy range, consistently cleaves the weakest protein:protein interfaces, producing products that are reflective of the known structure. We present here combined results for multiple complexes as a training set, two validation cases, and four computational models. We show that SID appearance energies can be predicted from structures via a computationally derived expression containing three terms (number of residues in a given interface, unsatisfied hydrogen bonds, and a rigidity factor).

Characterization of Protein Complexes using Targeted Proteomics

2014 ◽  
Vol 14 (3) ◽  
pp. 344-350 ◽  
Author(s):  
Yassel Gomez ◽  
Sebastien Gallien ◽  
Vivian Huerta ◽  
Jan Oostrum ◽  
Bruno Domon ◽  
...  
Keyword(s):  
Protein Complexes ◽  
Targeted Proteomics

Theology in the Church of England

2017 ◽  
Author(s):  
B. W. Young
Keyword(s):  
Eighteenth Century ◽  
Church Of England ◽  
Ecclesiastical History ◽  
International Reputation ◽  
History Of ◽  
Joseph Butler ◽  
Anglican Theology ◽  
The Many ◽  
The Church

The dismissive characterization of Anglican divinity between 1688 and 1800 as defensive and rationalistic, made by Mark Pattison and Leslie Stephen, has proved more enduring than most other aspects of a Victorian critique of the eighteenth-century Church of England. By directly addressing the analytical narratives offered by Pattison and Stephen, this chapter offers a comprehensive re-evaluation of this neglected period in the history of English theology. The chapter explores the many contributions to patristic study, ecclesiastical history, and doctrinal controversy made by theologians with a once deservedly international reputation: William Cave, Richard Bentley, William Law, William Warburton, Joseph Butler, George Berkeley, and William Paley were vitalizing influences on Anglican theology, all of whom were systematically depreciated by their agnostic Victorian successors. This chapter offers a revisionist account of the many achievements in eighteenth-century Anglican divinity.

scholarly journals Protein complex formation in methionine chain-elongation and leucine biosynthesis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Li-Qun Chen ◽  
Shweta Chhajed ◽  
Tong Zhang ◽  
Joseph M. Collins ◽  
Qiuying Pang ◽  
...  
Keyword(s):  
Protein Complexes ◽  
Complete Characterization ◽  
Bimolecular Fluorescence Complementation ◽  
Chain Elongation ◽  
Substrate Channeling ◽  
Leucine Biosynthesis ◽  
Protein Complex Formation ◽  
Genes Encoding ◽  
Isopropylmalate Dehydrogenase

AbstractDuring the past two decades, glucosinolate (GLS) metabolic pathways have been under extensive studies because of the importance of the specialized metabolites in plant defense against herbivores and pathogens. The studies have led to a nearly complete characterization of biosynthetic genes in the reference plant Arabidopsis thaliana. Before methionine incorporation into the core structure of aliphatic GLS, it undergoes chain-elongation through an iterative three-step process recruited from leucine biosynthesis. Although enzymes catalyzing each step of the reaction have been characterized, the regulatory mode is largely unknown. In this study, using three independent approaches, yeast two-hybrid (Y2H), coimmunoprecipitation (Co-IP) and bimolecular fluorescence complementation (BiFC), we uncovered the presence of protein complexes consisting of isopropylmalate isomerase (IPMI) and isopropylmalate dehydrogenase (IPMDH). In addition, simultaneous decreases in both IPMI and IPMDH activities in a leuc:ipmdh1 double mutants resulted in aggregated changes of GLS profiles compared to either leuc or ipmdh1 single mutants. Although the biological importance of the formation of IPMI and IPMDH protein complexes has not been documented in any organisms, these complexes may represent a new regulatory mechanism of substrate channeling in GLS and/or leucine biosynthesis. Since genes encoding the two enzymes are widely distributed in eukaryotic and prokaryotic genomes, such complexes may have universal significance in the regulation of leucine biosynthesis.

The development of body and organ shape

BMC Zoology ◽  
2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Ansa E. Cobham ◽  
Christen K. Mirth
Keyword(s):  
Relative Position ◽  
Body Shape ◽  
Single Cells ◽  
The Other ◽  
Geometric Features ◽  
Main Text ◽  
Size Characterization ◽  
Organ Shape ◽  
The Many

Abstract Background Organisms show an incredibly diverse array of body and organ shapes that are both unique to their taxon and important for adapting to their environment. Achieving these specific shapes involves coordinating the many processes that transform single cells into complex organs, and regulating their growth so that they can function within a fully-formed body. Main text Conceptually, body and organ shape can be separated in two categories, although in practice these categories need not be mutually exclusive. Body shape results from the extent to which organs, or parts of organs, grow relative to each other. The patterns of relative organ size are characterized using allometry. Organ shape, on the other hand, is defined as the geometric features of an organ’s component parts excluding its size. Characterization of organ shape is frequently described by the relative position of homologous features, known as landmarks, distributed throughout the organ. These descriptions fall into the domain of geometric morphometrics. Conclusion In this review, we discuss the methods of characterizing body and organ shape, the developmental programs thought to underlie each, highlight when and how the mechanisms regulating body and organ shape might overlap, and provide our perspective on future avenues of research.

scholarly journals Frequent assembly of chimeric complexes in the protein interaction network of an interspecies yeast hybrid

2020 ◽  
Author(s):  
Rohan Dandage ◽  
Caroline M Berger ◽  
Isabelle Gagnon-Arsenault ◽  
Kyung-Mee Moon ◽  
Richard Greg Stacey ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Molecular Level ◽  
Yeast Species ◽  
Protein Complexes ◽  
Mitochondrial Protein ◽  
Chimeric Protein ◽  
Interaction Network ◽  
Protein Protein Interactions ◽  
Extreme Phenotypes ◽  
Yeast Hybrid

Abstract Hybrids between species often show extreme phenotypes, including some that take place at the molecular level. In this study, we investigated the phenotypes of an interspecies diploid hybrid in terms of protein-protein interactions inferred from protein correlation profiling. We used two yeast species, Saccharomyces cerevisiae and Saccharomyces uvarum, which are interfertile, but yet have proteins diverged enough to be differentiated using mass spectrometry. Most of the protein-protein interactions are similar between hybrid and parents, and are consistent with the assembly of chimeric complexes, which we validated using an orthogonal approach for the prefoldin complex. We also identified instances of altered protein-protein interactions in the hybrid, for instance in complexes related to proteostasis and in mitochondrial protein complexes. Overall, this study uncovers the likely frequent occurrence of chimeric protein complexes with few exceptions, which may result from incompatibilities or imbalances between the parental proteins.

scholarly journals Grounding semantic transparency in context

Morphology ◽  
2021 ◽  
Author(s):  
Rossella Varvara ◽  
Gabriella Lapesa ◽  
Sebastian Padó
Keyword(s):  
Large Scale ◽  
Point Of View ◽  
Distributional Semantics ◽  
Semantic Transparency ◽  
Inclusion Measure ◽  
The Difference ◽  
Semantic Point ◽  
The Many ◽  
The Relationship

AbstractWe present the results of a large-scale corpus-based comparison of two German event nominalization patterns: deverbal nouns in -ung (e.g., die Evaluierung, ‘the evaluation’) and nominal infinitives (e.g., das Evaluieren, ‘the evaluating’). Among the many available event nominalization patterns for German, we selected these two because they are both highly productive and challenging from the semantic point of view. Both patterns are known to keep a tight relation with the event denoted by the base verb, but with different nuances. Our study targets a better understanding of the differences in their semantic import.The key notion of our comparison is that of semantic transparency, and we propose a usage-based characterization of the relationship between derived nominals and their bases. Using methods from distributional semantics, we bring to bear two concrete measures of transparency which highlight different nuances: the first one, cosine, detects nominalizations which are semantically similar to their bases; the second one, distributional inclusion, detects nominalizations which are used in a subset of the contexts of the base verb. We find that only the inclusion measure helps in characterizing the difference between the two types of nominalizations, in relation with the traditionally considered variable of relative frequency (Hay, 2001). Finally, the distributional analysis allows us to frame our comparison in the broader coordinates of the inflection vs. derivation cline.

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