scholarly journals Chemical Decorations of “MARs” Residents in Orchestrating Eukaryotic Gene Regulation

2020 ◽  
Vol 8 ◽  
Author(s):  
Tanaya Roychowdhury ◽  
Samit Chattopadhyay
Keyword(s):  
Gene Regulation ◽  
Conformational Changes ◽  
Protein Interactions ◽  
Protein Function ◽  
Functional Outcomes ◽  
Three Dimensional ◽  
Limited Information ◽  
Post Translational Modification ◽  
Cellular Functions ◽  
3D Matrix

Genome organization plays a crucial role in gene regulation, orchestrating multiple cellular functions. A meshwork of proteins constituting a three-dimensional (3D) matrix helps in maintaining the genomic architecture. Sequences of DNA that are involved in tethering the chromatin to the matrix are called scaffold/matrix attachment regions (S/MARs), and the proteins that bind to these sequences and mediate tethering are termed S/MAR-binding proteins (S/MARBPs). The regulation of S/MARBPs is important for cellular functions and is altered under different conditions. Limited information is available presently to understand the structure–function relationship conclusively. Although all S/MARBPs bind to DNA, their context- and tissue-specific regulatory roles cannot be justified solely based on the available information on their structures. Conformational changes in a protein lead to changes in protein–protein interactions (PPIs) that essentially would regulate functional outcomes. A well-studied form of protein regulation is post-translational modification (PTM). It involves disulfide bond formation, cleavage of precursor proteins, and addition or removal of low-molecular-weight groups, leading to modifications like phosphorylation, methylation, SUMOylation, acetylation, PARylation, and ubiquitination. These chemical modifications lead to varied functional outcomes by mechanisms like modifying DNA–protein interactions and PPIs, altering protein function, stability, and crosstalk with other PTMs regulating subcellular localizations. S/MARBPs are reported to be regulated by PTMs, thereby contributing to gene regulation. In this review, we discuss the current understanding, scope, disease implications, and future perspectives of the diverse PTMs regulating functions of S/MARBPs.

scholarly journals iProteinDB: an integrative database of Drosophila post-translational modifications

2018 ◽  
Author(s):  
Yanhui Hu ◽  
Richelle Sopko ◽  
Verena Chung ◽  
Romain A. Studer ◽  
Sean D. Landry ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Protein Function ◽  
Large Scale ◽  
Model Organisms ◽  
General Strategy ◽  
Post Translational Modification ◽  
Post Translational Modifications ◽  
Functional Sites ◽  
Evolutionarily Conserved ◽  
And Function

AbstractPost-translational modification (PTM) serves as a regulatory mechanism for protein function, influencing stability, protein interactions, activity and localization, and is critical in many signaling pathways. The best characterized PTM is phosphorylation, whereby a phosphate is added to an acceptor residue, commonly serine, threonine and tyrosine. As proteins are often phosphorylated at multiple sites, identifying those sites that are important for function is a challenging problem. Considering that many phosphorylation sites may be non-functional, prioritizing evolutionarily conserved phosphosites provides a general strategy to identify the putative functional sites with regards to regulation and function. To facilitate the identification of conserved phosphosites, we generated a large-scale phosphoproteomics dataset from Drosophila embryos collected from six closely-related species. We built iProteinDB (https://www.flyrnai.org/tools/iproteindb/), a resource integrating these data with other high-throughput PTM datasets, including vertebrates, and manually curated information for Drosophila. At iProteinDB, scientists can view the PTM landscape for any Drosophila protein and identify predicted functional phosphosites based on a comparative analysis of data from closely-related Drosophila species. Further, iProteinDB enables comparison of PTM data from Drosophila to that of orthologous proteins from other model organisms, including human, mouse, rat, Xenopus laevis, Danio rerio, and Caenorhabditis elegans.

scholarly journals Water–protein interactions from high–resolution protein crystallography

2004 ◽  
Vol 359 (1448) ◽  
pp. 1191-1206 ◽  
Author(s):  
Masayoshi Nakasako
Keyword(s):  
Hydrogen Bond ◽  
Conformational Changes ◽  
Protein Interactions ◽  
Three Dimensional ◽  
Water Molecules ◽  
Aqueous Environment ◽  
Hydration Water ◽  
X Ray Crystallography ◽  
Physico Chemical ◽  
Domain Motions

To understand the role of water in life at molecular and atomic levels, structures and interactions at the protein–water interface have been investigated by cryogenic X–ray crystallography. The method enabled a much clearer visualization of definite hydration sites on the protein surface than at ambient temperature. Using the structural models of proteins, including several hydration water molecules, the characteristics in hydration structures were systematically analysed for the amount, the interaction geometries between water molecules and proteins, and the local and global distribution of water molecules on the surface of proteins. The tetrahedral hydrogen–bond geometry of water molecules in bulk solvent was retained at the interface and enabled the extension of a three–dimensional chain connection of a hydrogen–bond network among hydration water molecules and polar protein atoms over the entire surface of proteins. Networks of hydrogen bonds were quite flexible to accommodate and/or to regulate the conformational changes of proteins such as domain motions. The present experimental results may have profound implications in the understanding of the physico–chemical principles governing the dynamics of proteins in an aqueous environment and a discussion of why water is essential to life at a molecular level.

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.

scholarly journals Arf•GAPs as Regulators of the Actin Cytoskeleton—An Update

2019 ◽  
Vol 20 (2) ◽  
pp. 442 ◽  
Author(s):  
Christine Tanna ◽  
Louisa Goss ◽  
Calvin Ludwig ◽  
Pei-Wen Chen
Keyword(s):  
Protein Interactions ◽  
Cell Function ◽  
Critical Role ◽  
Focal Adhesions ◽  
Actin Dynamics ◽  
Protein Protein Interactions ◽  
Post Translational Modification ◽  
Cellular Functions ◽  
Binding Domains ◽  
Multiple Protein

Arf•GTPase-activating proteins (Arf•GAPs) control the activity of ADP-ribosylation factors (Arfs) by inducing GTP hydrolysis and participate in a diverse array of cellular functions both through mechanisms that are dependent on and independent of their Arf•GAP activity. A number of these functions hinge on the remodeling of actin filaments. Accordingly, some of the effects exerted by Arf•GAPs involve proteins known to engage in regulation of the actin dynamics and architecture, such as Rho family proteins and nonmuscle myosin 2. Circular dorsal ruffles (CDRs), podosomes, invadopodia, lamellipodia, stress fibers and focal adhesions are among the actin-based structures regulated by Arf•GAPs. Arf•GAPs are thus important actors in broad functions like adhesion and motility, as well as the specialized functions of bone resorption, neurite outgrowth, and pathogen internalization by immune cells. Arf•GAPs, with their multiple protein-protein interactions, membrane-binding domains and sites for post-translational modification, are good candidates for linking the changes in actin to the membrane. The findings discussed depict a family of proteins with a critical role in regulating actin dynamics to enable proper cell function.

scholarly journals Mass Spectrometry and Structural Biology Techniques in the Studies on the Coronavirus-Receptor Interaction

Molecules ◽  
2020 ◽  
Vol 25 (18) ◽  
pp. 4133
Author(s):  
Danuta Witkowska
Keyword(s):  
Mass Spectrometry ◽  
Conformational Changes ◽  
Protein Interactions ◽  
Three Dimensional ◽  
Cell Receptor ◽  
Receptor Protein ◽  
Receptor Interaction ◽  
S Protein ◽  
X Ray Crystallography ◽  
Huge Impact

Mass spectrometry and some other biophysical methods, have made substantial contributions to the studies on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and human proteins interactions. The most interesting feature of SARS-CoV-2 seems to be the structure of its spike (S) protein and its interaction with the human cell receptor. Mass spectrometry of spike S protein revealed how the glycoforms are distributed across the S protein surface. X-ray crystallography and cryo-electron microscopy made huge impact on the studies on the S protein and ACE2 receptor protein interaction, by elucidating the three-dimensional structures of these proteins and their conformational changes. The findings of the most recent studies in the scope of SARS-CoV-2-Human protein-protein interactions are described here.

scholarly journals Post-translational Regulation of Runx2 in Bone and Cartilage

2009 ◽  
Vol 88 (8) ◽  
pp. 693-703 ◽  
Author(s):  
J.H. Jonason ◽  
G. Xiao ◽  
M. Zhang ◽  
L. Xing ◽  
D. Chen
Keyword(s):  
Protein Interactions ◽  
Protein Function ◽  
Translational Regulation ◽  
Target Genes ◽  
Molecular Level ◽  
Bone Development ◽  
Cleidocranial Dysplasia ◽  
Protein Protein Interactions ◽  
Post Translational Modification ◽  
Multiple Levels

The Runx2 gene product is essential for mammalian bone development. In humans, Runx2 haploinsufficiency results in cleidocranial dysplasia, a skeletal disorder characterized by bone and dental abnormalities. At the molecular level, Runx2 acts as a transcription factor for genes expressed in hypertrophic chondrocytes and osteoblasts. Runx2 gene expression and protein function are regulated on multiple levels, including transcription, translation, and post-translational modification. Furthermore, Runx2 is involved in numerous protein-protein interactions, most of which either activate or repress transcription of target genes. In this review, we discuss expression of Runx2 during development as well as the post-translational regulation of Runx2 through modification by phosphorylation, ubiquitination, and acetylation.

scholarly journals Ubiquitin-Specific Proteases: Players in Cancer Cellular Processes

2021 ◽  
Vol 14 (9) ◽  
pp. 848
Author(s):  
Lucas Cruz ◽  
Paula Soares ◽  
Marcelo Correia
Keyword(s):  
Protein Function ◽  
Deubiquitinating Enzymes ◽  
Post Translational Modification ◽  
Cellular Functions ◽  
Cellular Targets ◽  
Cellular Processes ◽  
Protein Ubiquitination ◽  
Damage Repair ◽  
Ubiquitin Molecule

Ubiquitination represents a post-translational modification (PTM) essential for the maintenance of cellular homeostasis. Ubiquitination is involved in the regulation of protein function, localization and turnover through the attachment of a ubiquitin molecule(s) to a target protein. Ubiquitination can be reversed through the action of deubiquitinating enzymes (DUBs). The DUB enzymes have the ability to remove the mono- or poly-ubiquitination signals and are involved in the maturation, recycling, editing and rearrangement of ubiquitin(s). Ubiquitin-specific proteases (USPs) are the biggest family of DUBs, responsible for numerous cellular functions through interactions with different cellular targets. Over the past few years, several studies have focused on the role of USPs in carcinogenesis, which has led to an increasing development of therapies based on USP inhibitors. In this review, we intend to describe different cellular functions, such as the cell cycle, DNA damage repair, chromatin remodeling and several signaling pathways, in which USPs are involved in the development or progression of cancer. In addition, we describe existing therapies that target the inhibition of USPs.

scholarly journals Tau Post-translational Modifications: Dynamic Transformers of Tau Function, Degradation, and Aggregation

2021 ◽  
Vol 11 ◽  
Author(s):  
Carolina Alquezar ◽  
Shruti Arya ◽  
Aimee W. Kao
Keyword(s):  
Protein Interactions ◽  
Protein Function ◽  
Protein Localization ◽  
Critical Role ◽  
Protein Protein Interactions ◽  
Post Translational Modification ◽  
Post Translational Modifications ◽  
Tau Function ◽  
Potential Impact ◽  
Important Position

Post-translational modifications (PTMs) on tau have long been recognized as affecting protein function and contributing to neurodegeneration. The explosion of information on potential and observed PTMs on tau provides an opportunity to better understand these modifications in the context of tau homeostasis, which becomes perturbed with aging and disease. Prevailing views regard tau as a protein that undergoes abnormal phosphorylation prior to its accumulation into the toxic aggregates implicated in Alzheimer's disease (AD) and other tauopathies. However, the phosphorylation of tau may, in fact, represent part of the normal but interrupted function and catabolism of the protein. In addition to phosphorylation, tau undergoes another forms of post-translational modification including (but not limited to), acetylation, ubiquitination, glycation, glycosylation, SUMOylation, methylation, oxidation, and nitration. A holistic appreciation of how these PTMs regulate tau during health and are potentially hijacked in disease remains elusive. Recent studies have reinforced the idea that PTMs play a critical role in tau localization, protein-protein interactions, maintenance of levels, and modifying aggregate structure. These studies also provide tantalizing clues into the possibility that neurons actively choose how tau is post-translationally modified, in potentially competitive and combinatorial ways, to achieve broad, cellular programs commensurate with the distinctive environmental conditions found during development, aging, stress, and disease. Here, we review tau PTMs and describe what is currently known about their functional impacts. In addition, we classify these PTMs from the perspectives of protein localization, electrostatics, and stability, which all contribute to normal tau function and homeostasis. Finally, we assess the potential impact of tau PTMs on tau solubility and aggregation. Tau occupies an undoubtedly important position in the biology of neurodegenerative diseases. This review aims to provide an integrated perspective of how post-translational modifications actively, purposefully, and dynamically remodel tau function, clearance, and aggregation. In doing so, we hope to enable a more comprehensive understanding of tau PTMs that will positively impact future studies.

Sulfur: the heart of nitric oxide-dependent redox signalling

2019 ◽  
Vol 70 (16) ◽  
pp. 4279-4286 ◽  
Author(s):  
Saima Umbreen ◽  
Jibril Lubega ◽  
Gary J Loake
Keyword(s):  
Nitric Oxide ◽  
Protein Interactions ◽  
Protein Function ◽  
Protein Protein Interactions ◽  
Post Translational Modification ◽  
Redox Signalling ◽  
Signalling Molecule ◽  
Environmental Relations ◽  
Plant Pathogen Interactions ◽  
Modify Protein

Abstract Nitric oxide (NO), more benign than its more reactive and damaging related molecules, reactive oxygen species (ROS), is perfectly suited for duties as a redox signalling molecule. A key route for NO bioactivity is through S-nitrosation, the addition of an NO moiety to a protein Cys thiol (-SH). This redox-based, post-translational modification (PTM) can modify protein function analogous to more well established PTMs such as phosphorylation, for example by modulating enzyme activity, localization, or protein–protein interactions. At the heart of the underpinning chemistry associated with this PTM is sulfur. The emerging evidence suggests that S-nitrosation is integral to a myriad of plant biological processes embedded in both development and environmental relations. However, a role for S-nitrosation is perhaps most well established in plant–pathogen interactions.

Sign in / Sign up

Export Citation Format

Share Document