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The Landscape of Intertwined Associations in Homooligomeric Proteins.

ABSTRACT: We present an overview of the full repertoire of intertwined associations in homooligomeric proteins. This overview summarizes recent findings on the different categories of intertwined associations in known protein structures, their assembly modes, the properties of their interfaces, and their structural plasticity. Furthermore, the current body of knowledge on the so-called three-dimensional domain-swapped systems is reexamined in the context of the wider landscape of intertwined homooligomers, with a particular focus on the mechanistic aspects that underpin intertwined self-association processes in proteins. Insights gained from this integrated overview into the physical and biological roles of intertwining are highlighted.

SUBMITTER: Wodak SJ

PROVIDER: S-EPMC4576362 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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The Landscape of Intertwined Associations in Homooligomeric Proteins.

Wodak Shoshana J SJ Malevanets Anatoly A MacKinnon Stephen S SS

Biophysical journal 20150901 6

We present an overview of the full repertoire of intertwined associations in homooligomeric proteins. This overview summarizes recent findings on the different categories of intertwined associations in known protein structures, their assembly modes, the properties of their interfaces, and their structural plasticity. Furthermore, the current body of knowledge on the so-called three-dimensional domain-swapped systems is reexamined in the context of the wider landscape of intertwined homooligomers ...[more]

PMID: 26340815

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Project description:Globally, COVID-19 vaccines have emerged as a boon, especially during the severe pandemic phases to control the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, saving millions of lives. However, mixed responses to vaccination with breakthrough challenges provided a rationale to explore the immune responses generated postvaccination, which plausibly alter the subsequent course of infection. In this regard, we comprehensively profiled the nasopharyngeal transcriptomic signature of double-dose-vaccinated individuals with breakthrough infections in comparison to unvaccinated infected persons. The vaccinated individuals demonstrated a gross downregulation of ribosomal proteins along with immune response genes and transcription/translational machinery that methodically modulated the entire innate immune landscape toward immune tolerance, a feature of innate immune memory. This coordinated response was orchestrated through 17 transcription factors captured as differentially expressed in the vaccination breakthroughs, including epigenetic modulators of CHD1 and LMNB1 and several immune response effectors, with ELF1 emerging as one of the important transcriptional regulators of the antiviral innate immune response. Deconvolution algorithm using bulk gene expression data revealed decreased T-cell populations with higher expression of memory B cells in the vaccination breakthroughs. Thus, vaccination might synergize the innate immune response with humoral and T-cell correlates of protection to more rapidly clear SARS-CoV-2 infections and reduce symptoms within a shorter span of time. An important feature invariably noted after secondary vaccination is downregulation of ribosomal proteins, which might plausibly be an important factor arising from epigenetic reprogramming leading to innate immune tolerance. IMPORTANCE The development of multiple vaccines against SARS-CoV-2 infection is an unprecedented milestone achieved globally. Immunization of the mass population is a rigorous process for getting the pandemic under control, yet continuous challenges are being faced, one of them being breakthrough infections. This is the first study wherein the vaccination breakthrough cases of COVD-19 relative to unvaccinated infected individuals have been explored. In the context of vaccination, how do innate and adaptive immune responses correspond to SARS-CoV-2 infection? How do these responses culminate in a milder observable phenotype with shorter hospital stay in vaccination breakthrough cases compared with the unvaccinated? We identified a subdued transcriptional landscape in vaccination breakthroughs with decreased expression of a large set of immune and ribosomal proteins genes. We propose a module of innate immune memory, i.e., immune tolerance, which plausibly helps to explain the observed mild phenotype and fast recovery in vaccination breakthroughs.

Dataset Information

The Landscape of Intertwined Associations in Homooligomeric Proteins.

Publications

The Landscape of Intertwined Associations in Homooligomeric Proteins.

Similar Datasets

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