scholarly journals Post‐translational modifications of proteins associated with yeast peroxisome membrane: An essential mode of regulatory mechanism

2021 ◽  
Author(s):  
Terence Infant ◽  
Rachayeeta Deb ◽  
Suchetana Ghose ◽  
Shirisha Nagotu
Keyword(s):  
Regulatory Mechanism ◽  
Post Translational Modifications ◽  
Peroxisome Membrane

scholarly journals P300-mediated NEDD4 acetylation drives ebolavirus VP40 egress by enhancing NEDD4 ligase activity

2021 ◽  
Vol 17 (6) ◽  
pp. e1009616
Author(s):  
Linliang Zhang ◽  
Shixiong Zhou ◽  
Majuan Chen ◽  
Jie Yan ◽  
Yi Yang ◽  
...  
Keyword(s):  
Life Cycle ◽  
Matrix Protein ◽  
Ebola Virus ◽  
Regulatory Mechanism ◽  
Physiological Effect ◽  
Host Cells ◽  
Post Translational Modifications ◽  
Virus Life Cycle ◽  
The Matrix ◽  
Zaire Ebolavirus

The final stage of Ebola virus (EBOV) replication is budding from host cells, where the matrix protein VP40 is essential for driving this process. Many post-translational modifications such as ubiquitination are involved in VP40 egress, but acetylation has not been studied yet. Here, we characterize NEDD4 is acetylated at a conserved Lys667 mediated by the acetyltransferase P300 which drives VP40 egress process. Importantly, P300-mediated NEDD4 acetylation promotes NEDD4-VP40 interaction which enhances NEDD4 E3 ligase activity and is essential for the activation of VP40 ubiquitination and subsequent egress. Finally, we find that Zaire ebolavirus production is dramatically reduced in P300 knockout cell lines, suggesting that P300-mediated NEDD4 acetylation may have a physiological effect on Ebola virus life cycle. Thus, our study identifies an acetylation-dependent regulatory mechanism that governs VP40 ubiquitination and provides insights into how acetylation controls EBOV VP40 egress.

scholarly journals Regulatory Mechanism of Soluble Epoxide Hydrolase by Post‐Translational Modifications

2008 ◽  
Vol 22 (S1) ◽  
Author(s):  
Ayala R Luria ◽  
Hsing‐Ju Tsai ◽  
Anthony Lu ◽  
Christophe Morisseau ◽  
Bruce D Hammock
Keyword(s):  
Epoxide Hydrolase ◽  
Regulatory Mechanism ◽  
Soluble Epoxide Hydrolase ◽  
Post Translational Modifications

Phosphoproteomic Analysis of Spiroplasma eriocheiris and Crosstalk with Acetylome Reveals the Role of Post-Translational Modifications in Metabolism

2020 ◽  
Vol 17 (5) ◽  
pp. 392-403
Author(s):  
Peng Liu ◽  
Libo Hou ◽  
Min Liu ◽  
Xuechuan Xu ◽  
Qi Gao ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Protein Function ◽  
Regulatory Mechanism ◽  
Arginine Deiminase ◽  
Phosphorylation Sites ◽  
Post Translational Modifications ◽  
Protein Protein Interaction ◽  
Fundamental Biological Process ◽  
Cell Skeleton

Background: Post-translational modifications (PTMs) such as phosphorylation are an essential regulatory mechanism of protein function and associated with a range of biological processes beyond genome and transcriptome. Spiroplasma eriocheiris, a wall-less helical bacterium, is one of the smallest known self-replicating bacteria and a novel pathogen of freshwater crustacean. Methods: To study the physiological characteristics and regulatory mechanism of S. eriocheiris, the protein phosphorylation in the bacterium were systematically investigated by iTRAQ analyzed by LC-MS/MS. Data are available via ProteomeXchange with identifier PXD015055. Results: We identified 465 phosphorylation sites in 246 proteins involved in a broad spectrum of fundamental biological process ranging from regulation of metabolic pathways to protein synthesis. Notably, most proteins in glycolysis and all proteins in the arginine deiminase system were phosphorylated. Meanwhile, the cytoskeleton proteins (Fibril, Mrebs and ET-Tu) were all phosphorylated suggest that the phosphorylation also may play a crucial role in cell skeleton formation. We have got a lot of highly conserved proteins and phosphorylation sites by analysis, and those proteins or phosphorylation sites were mainly participated in glucose metabolism and protein synthesis. Crosstalk analysis with protein-protein interaction networks in relation to phosphorylated proteins and acetylated proteins found that the two PTMs are required for playing crucial roles in many physiological processes in S. eriocheiris. By comparing the relative positions of acetylation versus phosphorylation, we found that the two modifications often found close to proximity on the same protein. Conclusions: The results imply that there is previously unreported hidden role of phosphorylation that define the functional state of Spiroplasma.

scholarly journals TBK1-mediated phosphorylation of LC3C and GABARAP-L2 controls autophagosome shedding by ATG4 protease

2019 ◽  
Author(s):  
Lina Herhaus ◽  
Ramachandra M. Bhaskara ◽  
Alf Håkon Lystad ◽  
Anne Simonsen ◽  
Gerhard Hummer ◽  
...  
Keyword(s):  
Regulatory Mechanism ◽  
Critical Role ◽  
Autophagosome Formation ◽  
Post Translational Modifications ◽  
Regulatory Pathways ◽  
Unidirectional Flow ◽  
Phosphorylation Event ◽  
Cellular Components ◽  
Premature Removal ◽  
Catabolic Process

AbstractAutophagy is a highly conserved catabolic process through which defective or otherwise harmful cellular components are targeted for degradation via the lysosomal route. Regulatory pathways, involving post-translational modifications such as phosphorylation, play a critical role in controlling this tightly orchestrated process. Here, we demonstrate that TBK1 regulates autophagy by phosphorylating autophagy modifiers LC3C and GABARAP-L2 on surface-exposed serine residues (LC3C S93 and S96; GABARAP-L2 S87 and S88). This phosphorylation event impedes their binding to the processing enzyme ATG4 by destabilizing the complex. Phosphorylated LC3C/GABARAP-L2 cannot be removed from liposomes by ATG4 and are thus protected from ATG4-mediated premature removal from nascent autoph-agosomes. This ensures a steady coat of lipidated LC3C/GABARAP-L2 throughout the early steps in autophagosome formation and aids in maintaining a unidirectional flow of the autophagosome to the lysosome. Taken together, we present a new regulatory mechanism of autophagy, which influences the conjugation and de-conjugation of LC3C and GABARAP-L2 to autophagosomes by TBK1-mediated phosphorylation.

scholarly journals Rubisco lysine acetylation occurs at very low stoichiometry in mature Arabidopsis leaves: implications for regulation of enzyme function

2020 ◽  
Vol 477 (19) ◽  
pp. 3885-3896 ◽  
Author(s):  
Brendan M. O'Leary ◽  
Andrew P. Scafaro ◽  
Ricarda Fenske ◽  
Owen Duncan ◽  
Elke Ströher ◽  
...  
Keyword(s):  
Regulatory Mechanism ◽  
Biological Significance ◽  
Maximal Activity ◽  
Enzyme Function ◽  
Lysine Acetylation ◽  
Night Time ◽  
Bisphosphate Carboxylase ◽  
Post Translational Modifications ◽  
Catalytic Function

Multiple studies have shown ribulose-1,5-bisphosphate carboxylase/oxygenase (E.C. 4.1.1.39; Rubisco) to be subject to Lys-acetylation at various residues; however, opposing reports exist about the biological significance of these post-translational modifications. One aspect of the Lys-acetylation that has not been addressed in plants generally, or with Rubisco specifically, is the stoichiometry at which these Lys-acetylation events occur. As a method to ascertain which Lys-acetylation sites on Arabidopsis Rubisco might be of regulatory importance to its catalytic function in the Calvin–Benson cycle, we purified Rubisco from leaves in both the day and night-time and performed independent mass spectrometry based methods to determine the stoichiometry of Rubisco Lys-acetylation events. The results indicate that Rubisco is acetylated at most Lys residues, but each acetylation event occurs at very low stoichiometry. Furthermore, in vitro treatments that increased the extent of Lys-acetylation on purified Rubisco had no effect on Rubisco maximal activity. Therefore, we are unable to confirm that Lys-acetylation at low stoichiometries can be a regulatory mechanism controlling Rubisco maximal activity. The results highlight the need for further use of stoichiometry measurements when determining the biological significance of reversible PTMs like acetylation.

scholarly journals Lysine acetylation of cytoskeletal proteins: Emergence of an actin code

2020 ◽  
Vol 219 (12) ◽  
Author(s):  
Mu A ◽  
Casey J. Latario ◽  
Laura E. Pickrell ◽  
Henry N. Higgs
Keyword(s):  
Chromatin Remodeling ◽  
Actin Polymerization ◽  
Regulatory Mechanism ◽  
Mitochondrial Fission ◽  
Cytoskeletal Proteins ◽  
Multiple Roles ◽  
Lysine Acetylation ◽  
Post Translational Modifications ◽  
Cytoplasmic Actin ◽  
Downstream Effects

Reversible lysine acetylation of nuclear proteins such as histones is a long-established important regulatory mechanism for chromatin remodeling and transcription. In the cytoplasm, acetylation of a number of cytoskeletal proteins, including tubulin, cortactin, and the formin mDia2, regulates both cytoskeletal assembly and stability. More recently, acetylation of actin itself was revealed to regulate cytoplasmic actin polymerization through the formin INF2, with downstream effects on ER-to-mitochondrial calcium transfer, mitochondrial fission, and vesicle transport. This finding raises the possibility that actin acetylation, along with other post-translational modifications to actin, might constitute an “actin code,” similar to the “histone code” or “tubulin code,” controlling functional shifts to these central cellular proteins. Given the multiple roles of actin in nuclear functions, its modifications might also have important roles in gene expression.

Reading the phosphorylation code: binding of the 14-3-3 protein to multivalent client phosphoproteins

2020 ◽  
Vol 477 (7) ◽  
pp. 1219-1225 ◽  
Author(s):  
Nikolai N. Sluchanko
Keyword(s):  
Protein Function ◽  
Intrinsically Disordered Protein ◽  
Structural Basis ◽  
Major Protein ◽  
Post Translational Modifications ◽  
Protein Protein Interaction ◽  
Intrinsically Disordered ◽  
Biochemical Journal ◽  
Multiple Binding ◽  
And Control

Many major protein–protein interaction networks are maintained by ‘hub’ proteins with multiple binding partners, where interactions are often facilitated by intrinsically disordered protein regions that undergo post-translational modifications, such as phosphorylation. Phosphorylation can directly affect protein function and control recognition by proteins that ‘read’ the phosphorylation code, re-wiring the interactome. The eukaryotic 14-3-3 proteins recognizing multiple phosphoproteins nicely exemplify these concepts. Although recent studies established the biochemical and structural basis for the interaction of the 14-3-3 dimers with several phosphorylated clients, understanding their assembly with partners phosphorylated at multiple sites represents a challenge. Suboptimal sequence context around the phosphorylated residue may reduce binding affinity, resulting in quantitative differences for distinct phosphorylation sites, making hierarchy and priority in their binding rather uncertain. Recently, Stevers et al. [Biochemical Journal (2017) 474: 1273–1287] undertook a remarkable attempt to untangle the mechanism of 14-3-3 dimer binding to leucine-rich repeat kinase 2 (LRRK2) that contains multiple candidate 14-3-3-binding sites and is mutated in Parkinson's disease. By using the protein-peptide binding approach, the authors systematically analyzed affinities for a set of LRRK2 phosphopeptides, alone or in combination, to a 14-3-3 protein and determined crystal structures for 14-3-3 complexes with selected phosphopeptides. This study addresses a long-standing question in the 14-3-3 biology, unearthing a range of important details that are relevant for understanding binding mechanisms of other polyvalent proteins.

Dicarbonyl derived post-translational modifications: chemistry bridging biology and aging-related disease

2020 ◽  
Vol 64 (1) ◽  
pp. 97-110
Author(s):  
Christian Sibbersen ◽  
Mogens Johannsen
Keyword(s):  
Mass Spectrometry ◽  
Future Research ◽  
Amino Acid Residues ◽  
Post Translational Modification ◽  
Dicarbonyl Compounds ◽  
Protein Targets ◽  
Post Translational Modifications ◽  
Reactive Protein ◽  
Glycation End Products ◽  
Direct Mass Spectrometry

Abstract In living systems, nucleophilic amino acid residues are prone to non-enzymatic post-translational modification by electrophiles. α-Dicarbonyl compounds are a special type of electrophiles that can react irreversibly with lysine, arginine, and cysteine residues via complex mechanisms to form post-translational modifications known as advanced glycation end-products (AGEs). Glyoxal, methylglyoxal, and 3-deoxyglucosone are the major endogenous dicarbonyls, with methylglyoxal being the most well-studied. There are several routes that lead to the formation of dicarbonyl compounds, most originating from glucose and glucose metabolism, such as the non-enzymatic decomposition of glycolytic intermediates and fructosyl amines. Although dicarbonyls are removed continuously mainly via the glyoxalase system, several conditions lead to an increase in dicarbonyl concentration and thereby AGE formation. AGEs have been implicated in diabetes and aging-related diseases, and for this reason the elucidation of their structure as well as protein targets is of great interest. Though the dicarbonyls and reactive protein side chains are of relatively simple nature, the structures of the adducts as well as their mechanism of formation are not that trivial. Furthermore, detection of sites of modification can be demanding and current best practices rely on either direct mass spectrometry or various methods of enrichment based on antibodies or click chemistry followed by mass spectrometry. Future research into the structure of these adducts and protein targets of dicarbonyl compounds may improve the understanding of how the mechanisms of diabetes and aging-related physiological damage occur.

The challenge of detecting modifications on proteins

2020 ◽  
Vol 64 (1) ◽  
pp. 135-153 ◽  
Author(s):  
Lauren Elizabeth Smith ◽  
Adelina Rogowska-Wrzesinska
Keyword(s):  
Mass Spectrometry ◽  
Protein Function ◽  
Chemical Properties ◽  
Lysine Acetylation ◽  
Mass Determination ◽  
Post Translational Modifications ◽  
Site Specific ◽  
The Common

Abstract Post-translational modifications (PTMs) are integral to the regulation of protein function, characterising their role in this process is vital to understanding how cells work in both healthy and diseased states. Mass spectrometry (MS) facilitates the mass determination and sequencing of peptides, and thereby also the detection of site-specific PTMs. However, numerous challenges in this field continue to persist. The diverse chemical properties, low abundance, labile nature and instability of many PTMs, in combination with the more practical issues of compatibility with MS and bioinformatics challenges, contribute to the arduous nature of their analysis. In this review, we present an overview of the established MS-based approaches for analysing PTMs and the common complications associated with their investigation, including examples of specific challenges focusing on phosphorylation, lysine acetylation and redox modifications.

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