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Protein Solubility and Aggregation in Bacteria

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889199761 Year: Pages: 127 DOI: 10.3389/978-2-88919-976-1 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Microbiology
Added to DOAB on : 2016-01-19 14:05:46
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Abstract

Proteins suffer many conformational changes and interactions through their life, from their synthesis at ribosomes to their controlled degradation. Only folded and soluble proteins are functional. Thus, protein folding and solubility are controlled genetically, transcriptionally, and at the protein sequence level. In addition, a well-conserved cellular machinery assists the folding of polypeptides to avoid misfolding and ensure the attainment of soluble and functional structures. When these redundant protective strategies are overcome, misfolded proteins are recruited into aggregates. Recombinant protein production is an essential tool for the biotechnology industry and also supports expanding areas of basic and biomedical research, including structural genomics and proteomics. Although bacteria still represent a convenient production system, many recombinant polypeptides produced in prokaryotic hosts undergo irregular or incomplete folding processes that usually result in their accumulation as insoluble aggregates, narrowing thus the spectrum of protein-based drugs that are available in the biotechnology market. In fact, the solubility of bacterially produced proteins is of major concern in production processes, and many orthogonal strategies have been exploited to try to increase soluble protein yields. Importantly, contrary to the usual assumption that the bacterial aggregates formed during protein production are totally inactive, the presence of a fraction of molecules in a native-like structure in these assemblies endorse them with a certain degree of biological activity, a property that is allowing the use of bacteria as factories to produce new functional materials and catalysts. The protein embedded in intracellular bacterial deposits might display different conformations, but they are usually enriched in beta-sheet-rich assemblies resembling the amyloid fibrils characteristic of several human neurodegenerative diseases. This makes bacterial cells simple, but biologically relevant model systems to address the mechanisms behind amyloid formation and the cellular impact of protein aggregates. Interestingly, bacteria also exploit the structural principles behind amyloid formation for functional purposes such as adhesion or cytotoxicity. In the present research topic we collect papers addressing all the issues mentioned above from both the experimental and computational point of view.

Endoplasmic Reticulcum and Its Role in Tumor Immunity

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889197866 Year: Pages: 101 DOI: 10.3389/978-2-88919-786-6 Language: English
Publisher: Frontiers Media SA
Subject: Oncology --- Medicine (General)
Added to DOAB on : 2016-04-07 11:22:02
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The endoplasmic reticulum (ER) is an organelle crucial to many cellular functions and processes, including the mounting of T-cell immune responses. Indeed, the ER has a well-established central role in anti-tumor immunity. Perhaps best characterized is the role of the ER in the processing of antigen peptides and the subsequent peptide assembly into MHC class I and II molecules. Such MHC/tumor-derived peptide complexes are pivotal for the correct recognition of altered self or viral peptides and the subsequent clonal expansion of tumor-reactive T-cells. In line with the role of the ER in immunity, tumor-associated mutations in ER proteins, as well as ER protein content and localization can have both deleterious and advantageous effects on anti-tumor immune responses. For instance, loss of function of ER-aminopeptidases, that trim peptides to size for MHC, alter the MHC class I - peptide repertoire thereby critically and negatively affecting T-cell recognition. On the other hand, altered localization of ER proteins can have immune-promoting effects. Specifically, translocation of certain ER proteins to the cell surface has been shown to promote anti-tumor T-cell immunity by directing uptake of apoptotic tumor cells to professional antigen presenting cells, thereby facilitating anti-tumor T-cell immunity. These selected examples highlight a diverse and multi-faceted role of the ER in anti-tumor immunity. Molecular biological insights from the past decade have uncovered that ER components may affect tumor immunity and have invoked a variety of follow-up questions. For instance, how and why are ER proteins over-expressed in tumors? How do nucleotide and somatic mutations in ER chaperones/processing machinery affect the MHC/peptide complex and tumor cell immunogenicity? How do ER-proteins translocate to the cell surface? What if any is the potential role of extracellular ER protein in tumor immunotherapy/vaccines, and can they be delivered to the tumor cell surface by photodynamic therapy, anthracyclines or by other means? In this special research topics issue, we present basic and clinical research reports covering many aspects of ER proteins in cancer recognition by the immune system, therapy and drug development. We also present new insights into ER stress, signalling and homeostasis in immunogenic cell death in cancer, the effect of parasitic ER proteins on tumour growth, ER protein regulation of angiogenesis. A comprehensive series of articles highlight our understanding of an expanding avenue of tumour immunology and therapeutic development, which exploit a collection of proteins within the ER that are not obvious candidates for immunity against tumors.

Redox and Nitrosative Signaling in Cardiovascular System: From Physiological Response to Disease

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889457267 Year: Pages: 258 DOI: 10.3389/978-2-88945-726-7 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Physiology
Added to DOAB on : 2019-01-23 14:53:43
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The role of ROS/RNS signaling in cardiovascular functions and diseases is increasingly emerging in the last decades. The involvement of ROS/RNS in the control of a large number of cardiovascular functions like the regulation of the vascular tone, the control of blood pressure or myocyte excitation-contraction coupling and force development has been broadly investigated and in part clarified. On the other hand, many efforts have been focused in clarifying the redox mechanisms involved in cardiovascular diseases like ischemia/reperfusion injury, diabetes-associated cardiovascular dysfunctions, atherosclerosis or hypertension, just to mention the major ones. However, in most cases the two levels of investigation remain separate and not interlaced, failing in the attempt to provide a unified vision of the pathophysiologic mechanisms of cardiovascular diseases. The major aim of the Research Topic has been to collect original papers and review articles dealing with the issue from basic to translation research point of views. The topic includes contributions that highlight different interesting aspects of cardiovascular biology with an integrated approach useful for the development of new ideas and advancements in the field of redox signaling in the control of normal cardiovascular functions and their disruption in diseases.

Cell-Free Synthetic Biology

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ISBN: 9783039280223 9783039280230 Year: Pages: 152 DOI: 10.3390/books978-3-03928-023-0 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: General and Civil Engineering --- Technology (General)
Added to DOAB on : 2020-01-30 16:39:46
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Cell-free synthetic biology is in the spotlight as a powerful and rapid approach to characterize and engineer natural biological systems. The open nature of cell-free platforms brings an unprecedented level of control and freedom for design compared to in vivo systems. This versatile engineering toolkit is used for debugging biological networks, constructing artificial cells, screening protein library, prototyping genetic circuits, developing new drugs, producing metabolites, and synthesizing complex proteins including therapeutic proteins, toxic proteins, and novel proteins containing non-standard (unnatural) amino acids. The book consists of a series of reviews, protocols, benchmarks, and research articles describing the current development and applications of cell-free synthetic biology in diverse areas.

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