scholarly journals Chemical reporters for exploring protein acylation

2015 ◽  
Vol 43 (2) ◽  
pp. 253-261 ◽  
Author(s):  
Emmanuelle Thinon ◽  
Howard C. Hang
Keyword(s):  
Protein Interactions ◽  
Protein Function ◽  
Cell Signalling ◽  
Fluorescent Imaging ◽  
Proteomic Profiling ◽  
Protein Protein Interactions ◽  
Recognition Elements ◽  
Cellular Pathways ◽  
Long Chain ◽  
Protein Acylation

Proteins are acylated by a variety of metabolites that regulates many important cellular pathways in all kingdoms of life. Acyl groups in cells can vary in structure from the smallest unit, acetate, to modified long-chain fatty acids, all of which can be activated and covalently attached to diverse amino acid side chains and consequently modulate protein function. For example, acetylation of Lys residues can alter the charge state of proteins and generate new recognition elements for protein–protein interactions. Alternatively, long-chain fatty-acylation targets proteins to membranes and enables spatial control of cell signalling. To facilitate the analysis of protein acylation in biology, acyl analogues bearing alkyne or azide tags have been developed that enable fluorescent imaging and proteomic profiling of modified proteins using bioorthogonal ligation methods. Herein, we summarize the currently available acylation chemical reporters and highlight their utility to discover and quantify the roles of protein acylation in biology.

scholarly journals Universal Screening Methods and Applications of ThermoFluor®

2006 ◽  
Vol 11 (7) ◽  
pp. 854-863 ◽  
Author(s):  
Maxwell D. Cummings ◽  
Michael A. Farnum ◽  
Marina I. Nelen
Keyword(s):  
Protein Interactions ◽  
Protein Function ◽  
Protein Unfolding ◽  
Direct Detection ◽  
Functional Characterization ◽  
Screening Methods ◽  
Protein Protein Interactions ◽  
Protein Protein Interaction ◽  
Bacterial Enzyme ◽  
Research Problems

The genomics revolution has unveiled a wealth of poorly characterized proteins. Scientists are often able to produce milligram quantities of proteins for which function is unknown or hypothetical, based only on very distant sequence homology. Broadly applicable tools for functional characterization are essential to the illumination of these orphan proteins. An additional challenge is the direct detection of inhibitors of protein-protein interactions (and allosteric effectors). Both of these research problems are relevant to, among other things, the challenge of finding and validating new protein targets for drug action. Screening collections of small molecules has long been used in the pharmaceutical industry as 1 method of discovering drug leads. Screening in this context typically involves a function-based assay. Given a sufficient quantity of a protein of interest, significant effort may still be required for functional characterization, assay development, and assay configuration for screening. Increasingly, techniques are being reported that facilitate screening for specific ligands for a protein of unknown function. Such techniques also allow for function-independent screening with better characterized proteins. ThermoFluor®, a screening instrument based on monitoring ligand effects on temperature-dependent protein unfolding, can be applied when protein function is unknown. This technology has proven useful in the decryption of an essential bacterial enzyme and in the discovery of a series of inhibitors of a cancer-related, protein-protein interaction. The authors review some of the tools relevant to these research problems in drug discovery, and describe our experiences with 2 different proteins.

scholarly journals Genome-wide protein-protein interactions and protein function exploration in cyanobacteria

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Qi Lv ◽  
Weimin Ma ◽  
Hui Liu ◽  
Jiang Li ◽  
Huan Wang ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Protein Function ◽  
Protein Protein Interactions ◽  
Genome Wide

scholarly journals Insulin signalling: putting the G- in protein-protein interactions

2004 ◽  
Vol 380 (1) ◽  
pp. e11-e12 ◽  
Author(s):  
Craig C. MALBON
Keyword(s):  
Insulin Receptor ◽  
Cross Talk ◽  
Protein Interactions ◽  
Tyrosine Kinases ◽  
Cell Biology ◽  
Receptor Tyrosine Kinases ◽  
Insulin Signalling ◽  
Cell Signalling ◽  
Protein Protein Interactions ◽  
Proximal Point

Cell signalling via receptor tyrosine kinases, such as the insulin receptor, and via heterotrimeric G-proteins, such as Gαi, Gαs and Gαq family members, constitute two of most avidly studied paradigms in cell biology. That elements of these two populous signalling pathways must cross-talk to achieve proper signalling in the regulation of cell proliferation, differentiation and metabolism has been anticipated, but the evolution of our thinking and the analysis of such cross-talk have lagged behind the ever-expanding troupe of players and the recognition of multivalency as the rule, rather than the exception, in signalling biology. New insights have been provided by Kreuzer et al. in this issue of the Biochemical Journal, in which insulin is shown to provoke recruitment of Gαi-proteins to insulin-receptor-based complexes that can regulate the gain of insulin-receptor-catalysed autophosphorylation, a proximal point in the insulin-sensitive cascade of signalling. Understanding the convergence and cross-talk of signals from the receptor tyrosine kinases and G-protein-coupled receptor pathways in physical, spatial and temporal contexts will remain a major challenge of cell biology.

New advances in extracting and learning from protein–protein interactions within unstructured biomedical text data

2019 ◽  
Vol 3 (4) ◽  
pp. 357-369
Author(s):  
J. Harry Caufield ◽  
Peipei Ping
Keyword(s):  
Protein Interactions ◽  
Protein Function ◽  
Historical Context ◽  
Specific Protein ◽  
Basic Unit ◽  
Biomedical Text ◽  
Protein Protein Interactions ◽  
Text Data ◽  
Ppi Networks ◽  
Protein Functions

Abstract Protein–protein interactions, or PPIs, constitute a basic unit of our understanding of protein function. Though substantial effort has been made to organize PPI knowledge into structured databases, maintenance of these resources requires careful manual curation. Even then, many PPIs remain uncurated within unstructured text data. Extracting PPIs from experimental research supports assembly of PPI networks and highlights relationships crucial to elucidating protein functions. Isolating specific protein–protein relationships from numerous documents is technically demanding by both manual and automated means. Recent advances in the design of these methods have leveraged emerging computational developments and have demonstrated impressive results on test datasets. In this review, we discuss recent developments in PPI extraction from unstructured biomedical text. We explore the historical context of these developments, recent strategies for integrating and comparing PPI data, and their application to advancing the understanding of protein function. Finally, we describe the challenges facing the application of PPI mining to the text concerning protein families, using the multifunctional 14-3-3 protein family as an example.

scholarly journals Getting into position: the catalytic mechanisms of protein ubiquitylation

2004 ◽  
Vol 379 (3) ◽  
pp. 513-525 ◽  
Author(s):  
Lori A. PASSMORE ◽  
David BARFORD
Keyword(s):  
Protein Interactions ◽  
Regulatory Elements ◽  
Substrate Selection ◽  
Protein Protein Interactions ◽  
Different Types ◽  
Catalytic Mechanisms ◽  
Cellular Pathways ◽  
Ubiquitin Conjugating Enzymes ◽  
Insight Into

The role of protein ubiquitylation in the control of diverse cellular pathways has recently gained widespread attention. Ubiquitylation not only directs the targeted destruction of tagged proteins by the 26 S proteasome, but it also modulates protein activities, protein–protein interactions and subcellular localization. An understanding of the components involved in protein ubiquitylation (E1s, E2s and E3s) is essential to understand how specificity and regulation are conferred upon these pathways. Much of what we know about the catalytic mechanisms of protein ubiquitylation comes from structural studies of the proteins involved in this process. Indeed, structures of ubiquitin-activating enzymes (E1s) and ubiquitin-conjugating enzymes (E2s) have provided insight into their mechanistic details. E3s (ubiquitin ligases) contain most of the substrate specificity and regulatory elements required for protein ubiquitylation. Although several E3 structures are available, the specific mechanistic role of E3s is still unclear. This review will discuss the different types of ubiquitin signals and how they are generated. Recent advances in the field of protein ubiquitylation will be examined, including the mechanisms of E1, E2 and E3. In particular, we discuss the complexity of molecular recognition required to impose selectivity on substrate selection and topology of poly-ubiquitin chains.

scholarly journals SET7/9-dependent methylation of ARTD1 at K508 stimulates poly-ADP-ribose formation after oxidative stress

Open Biology ◽  
2013 ◽  
Vol 3 (10) ◽  
pp. 120173 ◽  
Author(s):  
Ingrid Kassner ◽  
Anneli Andersson ◽  
Monika Fey ◽  
Martin Tomas ◽  
Elisa Ferrando-May ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Protein Interactions ◽  
Protein Function ◽  
Dependent Manner ◽  
Protein Protein Interactions ◽  
Post Translational Modification ◽  
Target Proteins ◽  
Protein Methyltransferase

ADP-ribosyltransferase diphtheria toxin-like 1 (ARTD1, formerly PARP1) is localized in the nucleus, where it ADP-ribosylates specific target proteins. The post-translational modification (PTM) with a single ADP-ribose unit or with polymeric ADP-ribose (PAR) chains regulates protein function as well as protein–protein interactions and is implicated in many biological processes and diseases. SET7/9 (Setd7, KMT7) is a protein methyltransferase that catalyses lysine monomethylation of histones, but also methylates many non-histone target proteins such as p53 or DNMT1. Here, we identify ARTD1 as a new SET7/9 target protein that is methylated at K508 in vitro and in vivo . ARTD1 auto-modification inhibits its methylation by SET7/9, while auto-poly-ADP-ribosylation is not impaired by prior methylation of ARTD1. Moreover, ARTD1 methylation by SET7/9 enhances the synthesis of PAR upon oxidative stress in vivo . Furthermore, laser irradiation-induced PAR formation and ARTD1 recruitment to sites of DNA damage in a SET7/9-dependent manner. Together, these results reveal a novel mechanism for the regulation of cellular ARTD1 activity by SET7/9 to assure efficient PAR formation upon cellular stress.

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