scholarly journals Current Perspective on Dominant Negative Mutations: Trends, Scope and Relevance

2020 ◽  
Vol 11 (4) ◽  
pp. 12020-12036
Keyword(s):  
Protein Function ◽  
Dominant Negative ◽  
Great Promise ◽  
Full Potential ◽  
Biological Processes ◽  
Functional Aspects ◽  
Current Perspective ◽  
Protein Functions ◽  
Dominant Negative Mutations ◽  
Traditional Approaches

Despite the advancements in tools and technologies implicated in identifying and characterizing novel genes, there are still a significant number of unknown function proteins. Moreover, the practices employed in order to characterize such proteins have proven to be a futile exercise so far because of many limitations associated with such traditional approaches. Dominant-negative mutations have shown great promise in this direction as the introduction of mutation in the target protein may abolish the protein function and inhibit the function of the simultaneously expressed wild-type protein. These dominant mutations have broader applications in biological processes to study various proteins in terms of their functional aspects, etiological factors, and mechanism of action, paving the way to diagnose many dreadful diseases, including cancer. Considering these facts, the current review emphasizes utilizing the full potential of such dominant-negative mutations in deciphering protein functions and their broad-spectrum applications in biology.

The Applications of Clustering Methods in Predicting Protein Functions

2019 ◽  
Vol 16 (5) ◽  
pp. 354-358
Author(s):  
Weiyang Chen ◽  
Weiwei Li ◽  
Guohua Huang ◽  
Matthew Flavel
Keyword(s):  
Computational Methods ◽  
Protein Function ◽  
Protein Function Prediction ◽  
Function Prediction ◽  
Biological Processes ◽  
Clustering Methods ◽  
Protein Functions

Background: The understanding of protein function is essential to the study of biological processes. However, the prediction of protein function has been a difficult task for bioinformatics to overcome. This has resulted in many scholars focusing on the development of computational methods to address this problem. Objective: In this review, we introduce the recently developed computational methods of protein function prediction and assess the validity of these methods. We then introduce the applications of clustering methods in predicting protein functions.

Dominant-negative mutations in PPAR alpha are present in unselected human populations and have a metabolic signature

2018 ◽  
Author(s):  
Audrey Melvin ◽  
Brian Lam ◽  
Claudia Langenberg ◽  
Maura Agostini ◽  
Erik Schoenmakers ◽  
...  
Keyword(s):  
Dominant Negative ◽  
Human Populations ◽  
Ppar Alpha ◽  
Metabolic Signature ◽  
Dominant Negative Mutations

scholarly journals Dynamic cortical actin remodeling by ERM proteins controls BCR microcluster organization and integrity

2011 ◽  
Vol 208 (5) ◽  
pp. 1055-1068 ◽  
Author(s):  
Bebhinn Treanor ◽  
David Depoil ◽  
Andreas Bruckbauer ◽  
Facundo D. Batista
Keyword(s):  
Actin Cytoskeleton ◽  
B Cell ◽  
Protein Function ◽  
Actin Polymerization ◽  
Lymphocyte Activation ◽  
Dominant Negative ◽  
Temporary Increase ◽  
Cortical Actin ◽  
Erm Proteins ◽  
Diffusion Dynamics

Signaling microclusters are a common feature of lymphocyte activation. However, the mechanisms controlling the size and organization of these discrete structures are poorly understood. The Ezrin-Radixin-Moesin (ERM) proteins, which link plasma membrane proteins with the actin cytoskeleton and regulate the steady-state diffusion dynamics of the B cell receptor (BCR), are transiently dephosphorylated upon antigen receptor stimulation. In this study, we show that the ERM proteins ezrin and moesin influence the organization and integrity of BCR microclusters. BCR-driven inactivation of ERM proteins is accompanied by a temporary increase in BCR diffusion, followed by BCR immobilization. Disruption of ERM protein function using dominant-negative or constitutively active ezrin constructs or knockdown of ezrin and moesin expression quantitatively and qualitatively alters BCR microcluster formation, antigen aggregation, and downstream BCR signal transduction. Chemical inhibition of actin polymerization also altered the structure and integrity of BCR microclusters. Together, these findings highlight a crucial role for the cortical actin cytoskeleton during B cell spreading and microcluster formation and function.

A Survey for Predicting ATP Binding Residues of Proteins Using Machine Learning Methods

2021 ◽  
Vol 28 ◽  
Author(s):  
Yu-He Yang ◽  
Jia-Shu Wang ◽  
Shi-Shi Yuan ◽  
Meng-Lu Liu ◽  
Wei Su ◽  
...  
Keyword(s):  
Machine Learning ◽  
Protein Function ◽  
Vital Role ◽  
Atp Binding ◽  
Learning Methods ◽  
Machine Learning Methods ◽  
Protein Ligand Interactions ◽  
Protein Functions ◽  
Ligand Interactions ◽  
Binding Residues

: Protein-ligand interactions are necessary for majority protein functions. Adenosine-5’-triphosphate (ATP) is one such ligand that plays vital role as a coenzyme in providing energy for cellular activities, catalyzing biological reaction and signaling. Knowing ATP binding residues of proteins is helpful for annotation of protein function and drug design. However, due to the huge amounts of protein sequences influx into databases in the post-genome era, experimentally identifying ATP binding residues is cost-ineffective and time-consuming. To address this problem, computational methods have been developed to predict ATP binding residues. In this review, we briefly summarized the application of machine learning methods in detecting ATP binding residues of proteins. We expect this review will be helpful for further research.

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 Annotating proteins with generalized functional linkages

2008 ◽  
Vol 105 (46) ◽  
pp. 17700-17705 ◽  
Author(s):  
Richard Llewellyn ◽  
David S. Eisenberg
Keyword(s):  
Protein Function ◽  
Biological Process ◽  
Computational Method ◽  
Majority Voting ◽  
Target Protein ◽  
Biological Processes ◽  
Gene Products ◽  
Protein Protein Interaction ◽  
Protein Protein Interaction Networks

As genome sequencing outstrips the rate of high-quality, low-throughput biochemical and genetic experimentation, accurate annotation of protein function becomes a bottleneck in the progress of the biomolecular sciences. Most gene products are now annotated by homology, in which an experimentally determined function is applied to a similar sequence. This procedure becomes error-prone between more divergent sequences and can contaminate biomolecular databases. Here, we propose a computational method of assignment of function, termed Generalized Functional Linkages (GFL), that combines nonhomology-based methods with other types of data. Functional linkages describe pairwise relationships between proteins that work together to perform a biological task. GFL provides a Bayesian framework that improves annotation by arbitrating a competition among biological process annotations to best describe the target protein. GFL addresses the unequal strengths of functional linkages among proteins, the quality of existing annotations, and the similarity among them while incorporating available knowledge about the cellular location or individual molecular function of the target protein. We demonstrate GFL with functional linkages defined by an algorithm known as zorch that quantifies connectivity in protein–protein interaction networks. Even when using proteins linked only by indirect or high-throughput interactions, GFL predicts the biological processes of many proteins in Saccharomyces cerevisiae, improving the accuracy of annotation by 20% over majority voting.

scholarly journals Hemophagocytic lymphohistiocytosis caused by dominant-negative mutations in STXBP2 that inhibit SNARE-mediated membrane fusion

Blood ◽  
2015 ◽  
Vol 125 (10) ◽  
pp. 1566-1577 ◽  
Author(s):  
Waldo A. Spessott ◽  
Maria L. Sanmillan ◽  
Margaret E. McCormick ◽  
Nishant Patel ◽  
Joyce Villanueva ◽  
...  
Keyword(s):  
Membrane Fusion ◽  
Hemophagocytic Lymphohistiocytosis ◽  
Dominant Negative ◽  
Snare Complex ◽  
Complex Assembly ◽  
Mutant Proteins ◽  
Key Points ◽  
Lymphocyte Cytotoxicity ◽  
Dominant Negative Mutations

Key Points Monoallelic STXBP2 mutations affecting codon 65 impair lymphocyte cytotoxicity and contribute to hemophagocytic lymphohistiocytosis. Munc18-2R65Q/W mutant proteins function in a dominant-negative manner to impair membrane fusion and arrest SNARE-complex assembly.

scholarly journals Disaggregases, molecular chaperones that resolubilize protein aggregates

2015 ◽  
Vol 87 (2 suppl) ◽  
pp. 1273-1292 ◽  
Author(s):  
David Z. Mokry ◽  
Josielle Abrahão ◽  
Carlos H.I. Ramos
Keyword(s):  
Heat Shock ◽  
Molecular Chaperones ◽  
Protein Function ◽  
Protein Aggregates ◽  
Cell Physiology ◽  
Biological Processes ◽  
Loss Of Function ◽  
Prion Propagation ◽  
Shock Proteins

The process of folding is a seminal event in the life of a protein, as it is essential for proper protein function and therefore cell physiology. Inappropriate folding, or misfolding, can not only lead to loss of function, but also to the formation of protein aggregates, an insoluble association of polypeptides that harm cell physiology, either by themselves or in the process of formation. Several biological processes have evolved to prevent and eliminate the existence of non-functional and amyloidogenic aggregates, as they are associated with several human pathologies. Molecular chaperones and heat shock proteins are specialized in controlling the quality of the proteins in the cell, specifically by aiding proper folding, and dissolution and clearance of already formed protein aggregates. The latter is a function of disaggregases, mainly represented by the ClpB/Hsp104 subfamily of molecular chaperones, that are ubiquitous in all organisms but, surprisingly, have no orthologs in the cytosol of metazoan cells. This review aims to describe the characteristics of disaggregases and to discuss the function of yeast Hsp104, a disaggregase that is also involved in prion propagation and inheritance.

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