Redox based anti-oxidant systems in plants: biochemical and structural analyses

We provide in this paper a comparative biochemical and structural analysis of the major thiol oxidoreductases (thioredoxin and glutaredoxin) of photosynthetic organisms in relation with their reductases and with target proteins, especially those involved either in the detoxication of peroxides such as hydrogen peroxide (thiol-peroxidases) or in the repair of oxidized methionines in proteins (methionine sulfoxide reductases). Particular emphasis will be given to the catalytic and regeneration mechanisms used by these enzymes. In addition, the protein-protein interactions of these systems will be discussed, leading to an integrated view of the functioning of these systems in various plant sub-cellular compartments.     

Dormant origins as a built-in safeguard in eukaryotic DNA replication against genome instability and disease development

DNA replication is a prerequisite for cell proliferation, yet it can be increasingly challenging for a eukaryotic cell to faithfully duplicate its genome as its size and complexity expands. Dormant origins now emerge as a key component for cells to successfully accomplish such a demanding but essential task. In this perspective, we will first provide an overview of the fundamental processes eukaryotic cells have developed to regulate origin licensing and firing. With a special focus on mammalian systems, we will then highlight the role of dormant origins in preventing replication-associated genome instability and their functional interplay with proteins involved in the DNA damage repair response for tumor suppression. Lastly, deficiencies in the origin licensing machinery will be discussed in relation to their influence on stem cell maintenance and human diseases.     

Function and specificity of 14-3-3 proteins in the regulation of carbohydrate and nitrogen metabolism

Protein phosphorylation is key to the regulation of many proteins. Altered protein activity often requires the interaction of the phosphorylated protein with a class of "adapters" known as 14-3-3 proteins. This review will cover aspects of 14-3-3 interaction with key proteins of carbon and nitrogen metabolism such as nitrate reductase, glutamine synthetase and sucrose-phosphate synthase. It will also address 14-3-3 involvement in signal transduction pathways with emphasis on the regulation of plant metabolism. To date, 14-3-3 proteins have been identified and studied in many diverse systems, yielding a plethora of data, requiring careful analysis and interpretation. Problems such as these are not uncommon when dealing with multigene families. The number of isoforms makes the question of redundancy versus specificity of 14-3-3 proteins a crucial one. This issue is discussed in relation to structure, function and expression of 14-3-3 proteins.     

种子蛋白质与蛋白质组的研究

综述了种子蛋白质与蛋白质组的研究, 主要介绍了种子发育与形成、种子休眠与萌发、种子保存与活力以及种子与环境相互作用的蛋白质与蛋白质组的研究。同时阐述了当今蛋白质组学在种子研究中的应用以及所取得的成果, 并展望了种子蛋白质组学的发展方向, 种子生物学的研究将从基因水平走向整体水平, 因此环境因子与种子蛋白质的相互作用是研究的重点。运用蛋白质组学将能揭示蛋白质的功能并明晰种子的生命机制。     

种子蛋白质与蛋白质组的研究

综述了种子蛋白质与蛋白质组的研究,主要介绍了种子发育与形成、种子休眠与萌发、种子保存与活力以及种子与环境相互作用的蛋白质与蛋白质组的研究.同时阐述了当今蛋白质组学在种子研究中的应用以及所取得的成果,并展望了种子蛋白质组学的发展方向,种子生物学的研究将从基因水平走向整体水平,因此环境因子与种子蛋白质的相互作用是研究的重点.运用蛋白质组学将能揭示蛋白质的功能并明晰种子的生命机制.     

The roles of Orai and Stim in bone health and disease

Orai and Stim proteins are the mediators of calcium release-activated calcium signaling and are important in the regulation of bone homeostasis and disease. This includes separate regulatory systems controlling mesenchymal stem cell differentiation to form osteoblasts, which make bone, and differentiation and regulation of osteoclasts, which resorb bone. These systems will be described separately, and their integration and relation to other systems, including Orai and Stim in teeth, will be briefly discussed at the end of this review.     

Antioxidative activity of selected fruits and vegetables

Recent studies have demonstrated that dietary plants are rich source of antioxidants and can contribute to the protection from age-related diseases. The aim of our study was to determine the total antioxidant capacity of extracts from different kinds of fruits and vegetables, and to examine their inhibitory effect on the oxidative damage to proteins in vitro. For determination of antioxidant capacity we used two direct methods. Among the food materials chosen for the present study, blueberries and red beets gave the maximum antioxidant activity. The lowest activity was determined in pears and green beans. Some extracts were more active in one method, while their activity was lower using the other method. To investigate inhibitory effects of fruits and vegetables extracts on the oxidative damage to proteins in vitro, we induced the oxidative damage to plasma proteins by sodium hypochlorite leading to formation of carbonyl compounds detected by spectrophotometric method. All extracts of fruits and vegetables showed inhibitory activity on the oxidative damage to proteins with raspberries and leek as most effective. Results of this study will be useful as an aid for dietary choices to increase antioxidant intake and will allow the investigation of the relation between dietary antioxidants and oxidative stress-induced diseases.     

Say NO to neurodegeneration: role of S-nitrosylation in neurodegenerative disorders

Nitric oxide (NO) is an important signaling molecule that controls a wide range of biological processes. One of the signaling mechanisms of NO is through the S-nitrosylation of cysteine residues on proteins. S-nitrosylation is now regarded as an important redox signaling mechanism in the regulation of different cellular and physiological functions. However, deregulation of S-nitrosylation has also been linked to various human diseases such as neurodegenerative disorders. Nitrosative stress has long been considered as a major mediator in the development of neurodegeneration, but the molecular mechanism of how NO can contribute to neurodegeneration is not completely clear. Early studies suggested that nitration of proteins, which can induce protein aggregation might contribute to the neurodegenerative process. However, several recent studies suggest that S-nitrosylation of proteins that are important for neuronal survival contributes substantially in the development of various neurodegenerative disorders. Thus, in-depth understanding of the mechanism of neurodegeneration in relation to S-nitrosylation will be critical for the development of therapeutic treatment against these neurodegenerative diseases.     

Large-scale proteomic analysis of membrane proteins

Proteomic analysis of membrane proteins is a promising approach for the identification of novel drug targets and/or disease biomarkers. Despite notable technological developments, obstacles related to extraction and solublization of membrane proteins are encountered. A critical discussion of the different preparative methods of membrane proteins is offered in relation to downstream proteomic applications, mainly gel-based analyses and mass spectrometry. Frequently, unknown proteins are identified by high-throughput profiling of membrane proteins. In search for novel membrane proteins, analysis of protein sequences using computational tools is performed to predict the presence of transmembrane domains. This review also presents these bioinformatic tools with the human proteome as a case study. Along with technological innovations, advancements in the areas of sample preparation and computational prediction of membrane proteins will lead to exciting discoveries.     

Adsorption equilibrium of proteins on a dye-ligand adsorbent

Summary The effects of pH and ionic strength on adsorption of lysozyme and bovine serum albumin to Blue Sepharose have been studied. Isotherms for both proteins obey the Freundlich model. Lysozyme binding involves both hydrophobic and cation exchange interactions with the adsorbent, while binding of albumin is due primarily to cation exchange. Protein properties will be discussed in relation to the binding patterns.     

Collectrin and ACE2 in renal and intestinal amino acid transport

Neutral amino acid transporters of the SLC6 family are expressed at the apical membrane of kidney and/or small intestine, where they (re-)absorb amino acids into the body.?In this review we present the results concerning the dependence of their apical expression with their association to partner proteins. We will in particular focus on the situation of B0AT1 and B0AT3, that associate with members of the renin-angiotensin system (RAS), namely Tmem27 and angiotensin-converting enzyme 2 (ACE2), in a tissue specific manner.?The role of this association in relation to the formation of a functional unit related to Na+ or amino acid transport will be assessed. We will conclude with some remarks concerning the relevance of this association to Hartnup disorder, where some mutations have been shown to differentially interact with the partner proteins.     

Collectrin and ACE2 in renal and intestinal amino acid transport

Neutral amino acid transporters of the SLC6 family are expressed at the apical membrane of kidney and/or small intestine, where they (re-)absorb amino acids into the body. In this review we present the results concerning the dependence of their apical expression with their association to partner proteins. We will in particular focus on the situation of B0AT1 and B0AT3, that associate with members of the renin-angiotensin system (RAS), namely Tmem27 and angiotensin-converting enzyme 2 (ACE2), in a tissue specific manner. The role of this association in relation to the formation of a functional unit related to Na+ or amino acid transport will be assessed. We will conclude with some remarks concerning the relevance of this association to Hartnup disorder, where some mutations have been shown to differentially interact with the partner proteins.     

Large-scale proteomic analysis of membrane proteins

Proteomic analysis of membrane proteins is a promising approach for the identification of novel drug targets and/or disease biomarkers. Despite notable technological developments, obstacles related to extraction and solublization of membrane proteins are encountered. A critical discussion of the different preparative methods of membrane proteins is offered in relation to downstream proteomic applications, mainly gel-based analyses and mass spectrometry. Frequently, unknown proteins are identified by high-throughput profiling of membrane proteins. In search for novel membrane proteins, analysis of protein sequences using computational tools is performed to predict the presence of transmembrane domains. This review also presents these bioinformatic tools with the human proteome as a case study. Along with technological innovations, advancements in the areas of sample preparation and computational prediction of membrane proteins will lead to exciting discoveries.     

Designing proteins to crystallize through beta-strand pairing

Inherent difficulties in growing protein crystals are major concerns within structural biology and particularly in structural proteomics. Here, we describe a novel approach of engineering target proteins by surface mutagenesis to increase the odds of crystallizing the molecules. To this end, we have exploited our recent triad-hypothesis using proteins with crystallographically defined beta-structures as the principal models. Crystal packing analyses of 182 protein structures belonging to 21 different superfamilies implied that the propensities to crystallize could be engineered into target proteins by replacing short segments, 5-6 residues, of their beta-strands with 'cassettes' of suitable packing motifs. These packing motifs will generate specific crystal packing interactions that promote crystallization. Key features of the primary and tertiary structures of such packing motifs have been identified for immunoglobulins. Further, packing motifs have been engineered successfully into six model antibodies without disturbing their capabilities to be produced, their immunoreactivity and their overall structure. Preliminary crystallization analyses have also been performed. Taken together, the procedures outline a rational protocol for crystallizing proteins by surface mutagenesis. The importance of these findings is discussed in relation to the crystallization of proteins in general.     

Association of actin with alpha crystallins

The alpha crystallins are cytosolic proteins that co-localize and co-purify with actin-containing microfilaments. Affinity column chromatography employing both covalently-coupled actin or alpha crystallin was used to demonstrate specific and saturable binding of actin with alpha crystallin. This conclusion was confirmed by direct visualization of alpha aggregates bound to actin polymerized in vitro. The significance of this interaction in relation to the functional properties of these two polypeptides will be discussed.     

Livin与恶性肿瘤的关系

livin属于凋亡抑制蛋白基因家族,与恶性肿瘤发生发展关系密切。根据livin基因结构特点,Livin可能参与调控胱蛋白天冬酶信号通路、丝裂原激活蛋白激酶途径,参与Wnt／beta-catenin信号通路。探讨了Livin与恶性黑色素瘤、膀胱癌、肺癌等多种恶性肿瘤的关系,为临床治疗这些疾病提供新的方法和思路。     

Cardiac contractile proteins and autoimmune myocarditis

Concerning cardiac contractile proteins, antigenicity and myocarditogenicity were discussed. In normal states, these proteins are immunologically tolerant, and can not provoke any heart-specific disease. Why the proteins can provoke such lethal autoimmune myocarditis has not been completely elucidated. Shortly after cardiac infection or myocardial ischemia, these proteins may work as the antigen for the autoimmune myocardites. First of all, the role of cardiac myosin has been strongly emphasized. But, the antigen determinants: epitope proteins remain unclear. Either cross-activity to the streptococcal M protein and/or the -helical coiled-coil protein may be an important factor to determine antigenicity. In this autoimmune myocarditis, the roles of T-lymphocyte and cardiac dendritic cell are noticeable. Through further study on the relation between antigen epitope and the infectious agents in the heart; on cardio-cytotoxity of the T-lymphocyte and on the precise contribution of cardiac dendritic cells, this autoimmune myocarditis will be more clarified.     

Antioxidant enzymes as redox-based biomarkers: a brief review

The field of redox proteomics focuses to a large extent on analyzing cysteine oxidation in proteins under different experimental conditions and states of diseases. The identification and localization of oxidized cysteines within the cellular milieu is critical for understanding the redox regulation of proteins under physiological and pathophysiological conditions, and it will in turn provide important information that are potentially useful for the development of novel strategies in the treatment and prevention of diseases associated with oxidative stress. Antioxidant enzymes that catalyze oxidation/reduction processes are able to serve as redox biomarkers in various human diseases, and they are key regulators controlling the redox state of functional proteins. Redox regulators with antioxidant properties related to active mediators, cellular organelles, and the surrounding environments are all connected within a network and are involved in diseases related to redox imbalance including cancer, ischemia/reperfusion injury, neurodegenerative diseases, as well as normal aging. In this review, we will briefly look at the selected aspects of oxidative thiol modification in antioxidant enzymes and thiol oxidation in proteins affected by redox control of antioxidant enzymes and their relation to disease. [BMB Reports 2015; 48(4): 200-208]