scholarly journals Alternating Phosphorylation with O-GlcNAc Modification: Another Way to Control Protein Function

10.5772/38821 ◽  
2012 ◽  
Author(s):  
Victor V. ◽  
Rita C.
Keyword(s):  
Protein Function ◽  
Control Protein

Optobiochemistry: Genetically Encoded Control of Protein Activity by Light

2021 ◽  
Vol 90 (1) ◽  
Author(s):  
Jihye Seong ◽  
Michael Z. Lin
Keyword(s):  
Protein Function ◽  
Living Cells ◽  
Optical Methods ◽  
Annual Review ◽  
Publication Date ◽  
Protein Activity ◽  
Spatiotemporal Resolution ◽  
Protein Functions ◽  
Protein Classes ◽  
Control Protein

Optobiochemical control of protein activities allows the investigation of protein functions in living cells with high spatiotemporal resolution. Over the last two decades, numerous natural photosensory domains have been characterized and synthetic domains engineered and assembled into photoregulatory systems to control protein function with light.Here, we review the field of optobiochemistry, categorizing photosensory domains by chromophore, describing photoregulatory systems by mechanism of action, and discussing protein classes frequently investigated using optical methods. We also present examples of how spatial or temporal control of proteins in living cells has provided new insights not possible with traditional biochemical or cell biological techniques. Expected final online publication date for the Annual Review of Biochemistry, Volume 90 is June 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Hypoxia elicits broad and systematic changes in protein subcellular localization

2011 ◽  
Vol 301 (4) ◽  
pp. C913-C928 ◽  
Author(s):  
Robert Michael Henke ◽  
Ranita Ghosh Dastidar ◽  
Ajit Shah ◽  
Daniela Cadinu ◽  
Xiao Yao ◽  
...  
Keyword(s):  
Protein Function ◽  
Protein Localization ◽  
Cell Periphery ◽  
Protein Distribution ◽  
Yeast Saccharomyces Cerevisiae ◽  
Transcriptional Regulatory ◽  
Chromatin Remodeling Complexes ◽  
Oxygen Signaling ◽  
Cellular Compartments ◽  
Control Protein

Oxygen provides a crucial energy source in eukaryotic cells. Hence, eukaryotes ranging from yeast to humans have developed sophisticated mechanisms to respond to changes in oxygen levels. Regulation of protein localization, like protein modifications, can be an effective mechanism to control protein function and activity. However, the contribution of protein localization in oxygen signaling has not been examined on a genomewide scale. Here, we examine how hypoxia affects protein distribution on a genomewide scale in the model eukaryote, the yeast Saccharomyces cerevisiae . We demonstrate, by live cell imaging, that hypoxia alters the cellular distribution of 203 proteins in yeast. These hypoxia-redistributed proteins include an array of proteins with important functions in various organelles. Many of them are nuclear and are components of key regulatory complexes, such as transcriptional regulatory and chromatin remodeling complexes. Under hypoxia, these proteins are synthesized and retained in the cytosol. Upon reoxygenation, they relocalize effectively to their normal cellular compartments, such as the nucleus, mitochondria, endoplasmic reticulum, and cell periphery. The resumption of the normal cellular locations of many proteins can occur even when protein synthesis is inhibited. Furthermore, we show that the changes in protein distribution induced by hypoxia follow a slower trajectory than those induced by reoxygenation. These results show that the regulation of protein localization is a common and potentially dominant mechanism underlying oxygen signaling and regulation. These results may have broad implications in understanding oxygen signaling and hypoxia responses in higher eukaryotes such as humans.

scholarly journals Trimethyllysine: From Carnitine Biosynthesis to Epigenetics

2020 ◽  
Vol 21 (24) ◽  
pp. 9451
Author(s):  
Marijn N. Maas ◽  
Jordi C. J. Hintzen ◽  
Miriam R. B. Porzberg ◽  
Jasmin Mecinović
Keyword(s):  
Protein Function ◽  
Genetic Disorders ◽  
Enzymatic Reactions ◽  
Lysine Methylation ◽  
Nucleosome Assembly ◽  
Cellular Processes ◽  
Subsequent Effect ◽  
Control Protein ◽  
Epigenetic Processes

Trimethyllysine is an important post-translationally modified amino acid with functions in the carnitine biosynthesis and regulation of key epigenetic processes. Protein lysine methyltransferases and demethylases dynamically control protein lysine methylation, with each state of methylation changing the biophysical properties of lysine and the subsequent effect on protein function, in particular histone proteins and their central role in epigenetics. Epigenetic reader domain proteins can distinguish between different lysine methylation states and initiate downstream cellular processes upon recognition. Dysregulation of protein methylation is linked to various diseases, including cancer, inflammation, and genetic disorders. In this review, we cover biomolecular studies on the role of trimethyllysine in carnitine biosynthesis, different enzymatic reactions involved in the synthesis and removal of trimethyllysine, trimethyllysine recognition by reader proteins, and the role of trimethyllysine on the nucleosome assembly.

Allosteric Disulfide Bonds in Thrombosis and Thrombolysis.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4036-4036
Author(s):  
Philip J. Hogg
Keyword(s):  
Protein Function ◽  
Disulfide Bonds ◽  
Factor Viia ◽  
Fibronectin Type Iii ◽  
Redox Change ◽  
Integrin Beta3 ◽  
Fibronectin Type Iii Domain ◽  
Protease Activated Receptor 2 ◽  
Control Protein ◽  
Fibronectin Type

Abstract Allosteric disulfide bonds control protein function by mediating conformational change when they undergo reduction or oxidation. The known allosteric disulfides are characterized by a particular bond geometry, the -RHStaple. A number of thrombosis and thrombolysis proteins contain one or more disulfide bonds of this type. Tissue factor (TF) is the first haemostasis protein shown to be controlled by an allosteric disulfide, the Cys186-Cys209 bond in the membrane-proximal fibronectin type III domain. TF exists in three forms on the cell surface; a cryptic form that is inert, a coagulant form that binds factor VIIa to initiate coagulation, or a signaling form that binds VIIa and cleaves protease activated receptor 2 that functions in inflammation, tumor progression and angiogenesis. Reduction and oxidation of the Cys186-Cys209 bond is central to the transition between the three activities of TF. The redox state of the bond appears to be controlled by protein disulphide isomerase and NO. Plasmin(ogen), vitronectin, glycoprotein 1balpha, integrin beta3 and thrombomodulin also contain -RHStaple disulfides and there is circumstantial evidence that the function of these proteins may involve redox change of these disulfide bonds.

scholarly journals Control of Aptamer Function Using Radiofrequency Magnetic Field

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Kenichi Taira ◽  
Koichi Abe ◽  
Takayuki Ishibasi ◽  
Katsuaki Sato ◽  
Kazunori Ikebukuro
Keyword(s):  
Magnetic Field ◽  
Control System ◽  
Gold Nanoparticle ◽  
Inhibitory Activity ◽  
Protein Function ◽  
Local Heating ◽  
Activity Assay ◽  
Complementary Dna ◽  
Dna Strand ◽  
Control Protein

Remote control of aptamer function has allowed us to control protein function in space and time. Here, we propose a novel control system for aptamer function by radiofrequency magnetic field- (RFMF-) induced local heating of a gold nanoparticle conjugated with an aptamer. In this study, we used a 31-mer thrombin-binding aptamer (TBA), which can inhibit thrombin activity, as a model aptamer. We evaluated the RFMF control of the inhibitory activity of a gold nanoparticle-conjugated TBA. To evaluate the effect of RFMF on enzymatic activity, we utilized a complementary DNA strand that maintains the broken structure during the activity assay. We observed a decrease in the inhibitory activity of TBA after RFMF irradiation. It indicates that RFMF is capable of controlling the TBA structure. Because RFMF allows noninvasive control of aptamer function, this strategy is expected to be novel way of controlling aptamer drug activity.

scholarly journals Single-molecule and Single-cell Approaches in Molecular Bioengineering

2020 ◽  
Vol 74 (9) ◽  
pp. 704-709
Author(s):  
Michael A. Nash
Keyword(s):  
Single Molecule ◽  
Protein Function ◽  
High Throughput Screening ◽  
Protein Sequences ◽  
Structural Features ◽  
Functional Protein ◽  
Molecular Systems ◽  
Measurement Tools ◽  
And Function ◽  
Control Protein

Protein sequences inhabit a discrete set in macromolecular space with incredible capacity to treat human disease. Despite our ability to program and manipulate protein sequences, the vast majority of protein development efforts are still done heuristically without a unified set of guiding principles. This article highlights work in understanding biophysical stability and function of proteins, developing new biophysical measurement tools and building high-throughput screening platforms to explore functional protein sequences. We highlight two primary areas. First, molecular biomechanics is a subfield concerned with the response of proteins to mechanical forces, and how we can leverage mechanical force to control protein function. The second subfield investigates the use of polymers and hydrogels in protein engineering and directed evolution in pursuit of new molecular systems with therapeutic applications. These two subdisciplines complement each other by shedding light onto sequence and structural features that can be used to impart stability into therapeutic proteins.

scholarly journals Molecular recognition of S-nitrosothiol substrate by its cognate protein denitrosylase

2018 ◽  
Vol 294 (5) ◽  
pp. 1568-1578 ◽  
Author(s):  
Colin T. Stomberski ◽  
Hua-Lin Zhou ◽  
Liwen Wang ◽  
Focco van den Akker ◽  
Jonathan S. Stamler
Keyword(s):  
Protein Function ◽  
Mammalian Cells ◽  
Cell Types ◽  
Hek293 Cells ◽  
Protein Substrates ◽  
Minority Species ◽  
Metabolic Protein ◽  
Dynamic Equilibria ◽  
Control Protein ◽  
Cognate Protein

Protein S-nitrosylation mediates a large part of nitric oxide's influence on cellular function by providing a fundamental mechanism to control protein function across different species and cell types. At steady state, cellular S-nitrosylation reflects dynamic equilibria between S-nitrosothiols (SNOs) in proteins and small molecules (low-molecular-weight SNOs) whose levels are regulated by dedicated S-nitrosylases and denitrosylases. S-Nitroso-CoA (SNO-CoA) and its cognate denitrosylases, SNO-CoA reductases (SCoRs), are newly identified determinants of protein S-nitrosylation in both yeast and mammals. Because SNO-CoA is a minority species among potentially thousands of cellular SNOs, SCoRs must preferentially recognize this SNO substrate. However, little is known about the molecular mechanism by which cellular SNOs are recognized by their cognate enzymes. Using mammalian cells, molecular modeling, substrate-capture assays, and mutagenic analyses, we identified a single conserved surface Lys (Lys-127) residue as well as active-site interactions of the SNO group that mediate recognition of SNO-CoA by SCoR. Comparing SCoRK127Aversus SCoRWT HEK293 cells, we identified a SNO-CoA–dependent nitrosoproteome, including numerous metabolic protein substrates. Finally, we discovered that the SNO-CoA/SCoR system has a role in mitochondrial metabolism. Collectively, our findings provide molecular insights into the basis of specificity in SNO-CoA–mediated metabolic signaling and suggest a role for SCoR-regulated S-nitrosylation in multiple metabolic processes.

scholarly journals Global, quantitative and dynamic mapping of protein subcellular localization

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Daniel N Itzhak ◽  
Stefka Tyanova ◽  
Jürgen Cox ◽  
Georg HH Borner
Keyword(s):  
Subcellular Localization ◽  
Protein Function ◽  
Cell Biology ◽  
Dynamic Capabilities ◽  
Protein Translocation ◽  
Protein Localization ◽  
Quantitative Model ◽  
Dynamic Mapping ◽  
Global Mapping ◽  
Control Protein

Subcellular localization critically influences protein function, and cells control protein localization to regulate biological processes. We have developed and applied Dynamic Organellar Maps, a proteomic method that allows global mapping of protein translocation events. We initially used maps statically to generate a database with localization and absolute copy number information for over 8700 proteins from HeLa cells, approaching comprehensive coverage. All major organelles were resolved, with exceptional prediction accuracy (estimated at >92%). Combining spatial and abundance information yielded an unprecedented quantitative view of HeLa cell anatomy and organellar composition, at the protein level. We subsequently demonstrated the dynamic capabilities of the approach by capturing translocation events following EGF stimulation, which we integrated into a quantitative model. Dynamic Organellar Maps enable the proteome-wide analysis of physiological protein movements, without requiring any reagents specific to the investigated process, and will thus be widely applicable in cell biology.

Novel substrates and functions for the ubiquitin-like molecule NEDD8

2008 ◽  
Vol 36 (5) ◽  
pp. 802-806 ◽  
Author(s):  
Dimitris P. Xirodimas
Keyword(s):  
Cell Growth ◽  
Protein Function ◽  
Biological Significance ◽  
Molecular Targets ◽  
Precursor Cell ◽  
Present Review ◽  
Neural Precursor ◽  
The Novel ◽  
Neural Precursor Cell ◽  
Control Protein

Genetic experiments have established an important role for the ubiquitin-like molecule NEDD8 (neural-precursor-cell-expressed developmentally down-regulated 8) in the regulation of cell growth, viability and development. It is therefore essential to identify the molecular targets for the pathway. Until recently, the cullin family of proteins was characterized as the only substrates for NEDDylation. However, through either direct biological approaches or the use of proteomics, it is now evident that the NEDD8 proteome is more diverse than thought previously. The present review describes the biological significance of NEDDylation for the novel identified substrates and the emerging evidence for the co-operation between the ubiquitin and NEDD8 pathways to control protein function.

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