Production mechanisms, structural features and post-translational modifications of plant peptides

Background:: Many pathways regarding healthy cells and/or linked to diseases onset and progression depend on large assemblies including multi-protein complexes. Protein-protein interactions may occur through a vast array of modules known as protein interaction domains (PIDs). Objective:: This review concerns with PIDs recognizing post-translationally modified peptide sequences and intends to provide the scientific community with state of art knowledge on their 3D structures, binding topologies and potential applications in the drug discovery field. Method:: Several databases, such as the Pfam (Protein family), the SMART (Simple Modular Architecture Research Tool) and the PDB (Protein Data Bank), were searched to look for different domain families and gain structural information on protein complexes in which particular PIDs are involved. Recent literature on PIDs and related drug discovery campaigns was retrieved through Pubmed and analyzed. Results and Conclusion:: PIDs are rather versatile as concerning their binding preferences. Many of them recognize specifically only determined amino acid stretches with post-translational modifications, a few others are able to interact with several post-translationally modified sequences or with unmodified ones. Many PIDs can be linked to different diseases including cancer. The tremendous amount of available structural data led to the structure-based design of several molecules targeting protein-protein interactions mediated by PIDs, including peptides, peptidomimetics and small compounds. More studies are needed to fully role out, among different families, PIDs that can be considered reliable therapeutic targets, however, attacking PIDs rather than catalytic domains of a particular protein may represent a route to obtain selective inhibitors.

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Integration of Sugar Metabolism and Proteoglycan Synthesis by UDP-glucose Dehydrogenase

Journal of Histochemistry & Cytochemistry ◽

10.1369/0022155420947500 ◽

2020 ◽

Vol 69 (1) ◽

pp. 13-23 ◽

Cited By ~ 2

Author(s):

Brenna M. Zimmer ◽

Joseph J. Barycki ◽

Melanie A. Simpson

Keyword(s):

Glucose Dehydrogenase ◽

Sugar Metabolism ◽

Structural Features ◽

Proteoglycan Synthesis ◽

Allosteric Modulators ◽

Uridine Diphosphate ◽

Cellular Mechanisms ◽

Glycosaminoglycan Synthesis ◽

Post Translational Modifications ◽

Multiple Levels

Regulation of proteoglycan and glycosaminoglycan synthesis is critical throughout development, and to maintain normal adult functions in wound healing and the immune system, among others. It has become increasingly clear that these processes are also under tight metabolic control and that availability of carbohydrate and amino acid metabolite precursors has a role in the control of proteoglycan and glycosaminoglycan turnover. The enzyme uridine diphosphate (UDP)-glucose dehydrogenase (UGDH) produces UDP-glucuronate, an essential precursor for new glycosaminoglycan synthesis that is tightly controlled at multiple levels. Here, we review the cellular mechanisms that regulate UGDH expression, discuss the structural features of the enzyme, and use the structures to provide a context for recent studies that link post-translational modifications and allosteric modulators of UGDH to its function in downstream pathways:

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A structural view of PA2G4 isoforms with opposing functions in cancer

Journal of Biological Chemistry ◽

10.1074/jbc.rev120.014293 ◽

2020 ◽

Vol 295 (47) ◽

pp. 16100-16112

Author(s):

Brendan W. Stevenson ◽

Michael A. Gorman ◽

Jessica Koach ◽

Belamy B. Cheung ◽

Glenn M. Marshall ◽

...

Keyword(s):

Structural Features ◽

Cellular Growth ◽

Structure Based Drug Design ◽

Post Translational Modifications ◽

Protein Protein Interaction ◽

Interaction Sites ◽

Structure Relationship ◽

Relationship Of ◽

Functional Components

The role of proliferation-associated protein 2G4 (PA2G4), alternatively known as ErbB3-binding protein 1 (EBP1), in cancer has become apparent over the past 20 years. PA2G4 expression levels are correlated with prognosis in a range of human cancers, including neuroblastoma, cervical, brain, breast, prostate, pancreatic, hepatocellular, and other tumors. There are two PA2G4 isoforms, PA2G4-p42 and PA2G4-p48, and although both isoforms of PA2G4 regulate cellular growth and differentiation, these isoforms often have opposing roles depending on the context. Therefore, PA2G4 can function either as a contextual tumor suppressor or as an oncogene, depending on the tissue being studied. However, it is unclear how distinct structural features of the two PA2G4 isoforms translate into different functional outcomes. In this review, we examine published structures to identify important structural and functional components of PA2G4 and consider how they may explain its crucial role in the malignant phenotype. We will highlight the lysine-rich regions, protein-protein interaction sites, and post-translational modifications of the two PA2G4 isoforms and relate these to the functional cellular role of PA2G4. These data will enable a better understanding of the function and structure relationship of the two PA2G4 isoforms and highlight the care that will need to be undertaken for those who wish to conduct isoform-specific structure-based drug design campaigns.

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PRISMOID: a comprehensive 3D structure database for post-translational modifications and mutations with functional impact

Briefings in Bioinformatics ◽

10.1093/bib/bbz050 ◽

2019 ◽

Vol 21 (3) ◽

pp. 1069-1079 ◽

Cited By ~ 7

Author(s):

Fuyi Li ◽

Cunshuo Fan ◽

Tatiana T Marquez-Lago ◽

André Leier ◽

Jerico Revote ◽

...

Keyword(s):

Solvent Accessibility ◽

3D Structure ◽

Structural Features ◽

Biological Information ◽

High Definition ◽

Sequence Alignments ◽

Post Translational Modifications ◽

Functional Impact ◽

Structure Database ◽

Wide Range

Abstract Post-translational modifications (PTMs) play very important roles in various cell signaling pathways and biological process. Due to PTMs’ extremely important roles, many major PTMs have been studied, while the functional and mechanical characterization of major PTMs is well documented in several databases. However, most currently available databases mainly focus on protein sequences, while the real 3D structures of PTMs have been largely ignored. Therefore, studies of PTMs 3D structural signatures have been severely limited by the deficiency of the data. Here, we develop PRISMOID, a novel publicly available and free 3D structure database for a wide range of PTMs. PRISMOID represents an up-to-date and interactive online knowledge base with specific focus on 3D structural contexts of PTMs sites and mutations that occur on PTMs and in the close proximity of PTM sites with functional impact. The first version of PRISMOID encompasses 17 145 non-redundant modification sites on 3919 related protein 3D structure entries pertaining to 37 different types of PTMs. Our entry web page is organized in a comprehensive manner, including detailed PTM annotation on the 3D structure and biological information in terms of mutations affecting PTMs, secondary structure features and per-residue solvent accessibility features of PTM sites, domain context, predicted natively disordered regions and sequence alignments. In addition, high-definition JavaScript packages are employed to enhance information visualization in PRISMOID. PRISMOID equips a variety of interactive and customizable search options and data browsing functions; these capabilities allow users to access data via keyword, ID and advanced options combination search in an efficient and user-friendly way. A download page is also provided to enable users to download the SQL file, computational structural features and PTM sites’ data. We anticipate PRISMOID will swiftly become an invaluable online resource, assisting both biologists and bioinformaticians to conduct experiments and develop applications supporting discovery efforts in the sequence–structural–functional relationship of PTMs and providing important insight into mutations and PTM sites interaction mechanisms. The PRISMOID database is freely accessible at http://prismoid.erc.monash.edu/. The database and web interface are implemented in MySQL, JSP, JavaScript and HTML with all major browsers supported.

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Structure, Activity, and Function of the Protein Lysine Methyltransferase G9a

Life ◽

10.3390/life11101082 ◽

2021 ◽

Vol 11 (10) ◽

pp. 1082

Author(s):

Coralie Poulard ◽

Lara M. Noureddine ◽

Ludivine Pruvost ◽

Muriel Le Romancer

Keyword(s):

Transcriptional Repression ◽

Cancer Biology ◽

Structural Features ◽

Cellular Mechanisms ◽

Post Translational Modifications ◽

Structure Activity ◽

Lysine Residues ◽

Lysine Methyltransferase ◽

And Function ◽

Insight Into

G9a is a lysine methyltransferase catalyzing the majority of histone H3 mono- and dimethylation at Lys-9 (H3K9), responsible for transcriptional repression events in euchromatin. G9a has been shown to methylate various lysine residues of non-histone proteins and acts as a coactivator for several transcription factors. This review will provide an overview of the structural features of G9a and its paralog called G9a-like protein (GLP), explore the biochemical features of G9a, and describe its post-translational modifications and the specific inhibitors available to target its catalytic activity. Aside from its role on histone substrates, the review will highlight some non-histone targets of G9a, in order gain insight into their role in specific cellular mechanisms. Indeed, G9a was largely described to be involved in embryonic development, hypoxia, and DNA repair. Finally, the involvement of G9a in cancer biology will be presented.

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PRISMOID: a comprehensive 3D structure database for post-translational modifications and mutations with functional impact

10.1101/523308 ◽

2019 ◽

Cited By ~ 1

Author(s):

Fuyi Li ◽

Cunshuo Fan ◽

Tatiana T. Marquez-Lago ◽

André Leier ◽

Jerico Revote ◽

...

Keyword(s):

Solvent Accessibility ◽

3D Structure ◽

Structural Features ◽

Biological Information ◽

High Definition ◽

Sequence Alignments ◽

Post Translational Modifications ◽

Functional Impact ◽

Structure Database ◽

Wide Range

AbstractPost-translational modifications (PTMs) play very important roles in various cell signalling pathways and biological process. Due to PTMs’ extremely important roles, many major PTMs have been thoroughly studied, while the functional and mechanical characterization of major PTMs is well-documented in several databases. However, most currently available databases mainly focus on protein sequences, while the real 3D structures of PTMs have been largely ignored. Therefore, studies of PTMs 3D structural signatures have been severely limited by the deficiency of the data. Here, we develop PRISMOID, a novel publicly available and free 3D structure database for a wide range of PTMs. PRISMOID represents an up-to-date and interactive online knowledge base with specific focus on 3D structural contexts of PTMs sites and mutations that occur on PTMs and in the close proximity of PTM sites with functional impact. The first version of PRISMOID encompasses 17,145 non-redundant modification sites on 3,919 related protein 3D structure entries pertaining to 37 different types of PTMs. Our entry web page is organized in a comprehensive manner, including detailed PTM annotation on the 3D structure and biological information in terms of mutations affecting PTMs, secondary structure features and per-residue solvent accessibility features of PTM sites, domain context, predicted natively disordered regions and sequence alignments. In addition, high-definition JavaScript packages are employed to enhance information visualization in PRISMOID. PRISMOID equips a variety of interactive and customizable search options and data browsing functions; these capabilities allow users to access data via keyword, ID, and advanced options combination search in an efficient and user-friendly way. A download page is also provided to enable users to download the SQL file, computational structural features, and PTM sites’ data. We anticipate PRISMOID will swiftly become an invaluable online resource, assisting both biologists and bioinformaticians to conduct experiments and develop applications supporting discovery efforts in the sequence-structural-functional relationship of PTMs and providing important insight into mutations and PTM sites interaction mechanisms. The PRISMOID database is freely accessible at http://prismoid.erc.monash.edu/. The database and web interface are implemented in MySQL, JSP, JavaScript, and HTML with all major browsers supported.

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Regulation of Microtubule Disassembly by Spatially Heterogeneous Patterns of Acetylation

10.1101/725895 ◽

2019 ◽

Author(s):

J S Aparna ◽

Ranjith Padinhateeri ◽

Dibyendu Das

Keyword(s):

Spatial Patterns ◽

Computational Study ◽

Structural Features ◽

Lateral Interaction ◽

Cellular Functions ◽

Chemical Modifications ◽

Post Translational Modifications ◽

Cellular Processes ◽

The Stability ◽

Kinetics Of

AbstractMicrotubules (MTs) are bio-polymers, composed of tubulin proteins, involved in several functions such as cell division, transport of cargoes within cells, maintaining cellular structures etc. Their kinetics are often affected by chemical modifications on the filament known as Post Translational Modifications (PTMs). Acetylation is a PTM which occurs on the luminal surface of the MT lattice and has been observed to reduce the lateral interaction between tubulins on adjacent protofilaments. Depending on the properties of the acetylase enzyme αTAT1 and the structural features of MTs, the patterns of acetylation formed on MTs are observed to be quite diverse. In this study, we present a multi-protofilament model with spatially heterogenous patterns of acetylation, and investigate how the local kinetic differences arising from heterogeneity affect the global kinetics of MT filaments. From the computational study we conclude that a filament with spatially uniform acetylation is least stable against disassembly, while ones with more clustered acetylation patterns may provide better resistance against disassembly. The increase in disassembly times for clustered pattern as compared to uniform pattern can be upto fifty percent for identical amounts of acetylation. Given that acetylated MTs affect several cellular functions as well as diseases such as cancer, our study indicates that spatial patterns of acetylation need to be focussed on, apart from the overall amount of acetylation.Author SummaryMicrotubules (MTs) form a crucial part of the cytoskeletal machinery which regulates several cellular processes. The basic building block of MTs are tubulin proteins. These proteins assemble in lateral and longitudinal directions to form a hollow cylindrical structure of a MT. There are chemical modifications on tubulin, known as Post Translational Modifications (PTMs), which affect the stability and dynamics of MT filaments. We computationally study how one such PTM, namely acetylation, affects the kinetics of disassembly of a MT filament. We propose a model which incorporates spatially heterogeneous patterns of acetylation on MT filament and study how they may regulate the disassembly times and velocities, a factor hitherto unexplored in studies. We conclude that there are significant differences of disassembly velocities and their fluctuations depending on the differnces in spatial patterns of acetylation.

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TRPing to the Point of Clarity: Understanding the Function of the Complex TRPV4 Ion Channel

Cells ◽

10.3390/cells10010165 ◽

2021 ◽

Vol 10 (1) ◽

pp. 165

Author(s):

Trine L. Toft-Bertelsen ◽

Nanna MacAulay

Keyword(s):

Ion Channel ◽

Transient Receptor Potential ◽

Receptor Potential ◽

Structural Features ◽

Cation Channels ◽

Transient Receptor Potential Vanilloid ◽

Post Translational Modifications ◽

Disease States ◽

Health And Disease ◽

Transient Receptor

The transient receptor potential vanilloid 4 channel (TRPV4) belongs to the mammalian TRP superfamily of cation channels. TRPV4 is ubiquitously expressed, activated by a disparate array of stimuli, interacts with a multitude of proteins, and is modulated by a range of post-translational modifications, the majority of which we are only just beginning to understand. Not surprisingly, a great number of physiological roles have emerged for TRPV4, as have various disease states that are attributable to the absence, or abnormal functioning, of this ion channel. This review will highlight structural features of TRPV4, endogenous and exogenous activators of the channel, and discuss the reported roles of TRPV4 in health and disease.

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Functionalized Au15 nanoclusters as luminescent probes for protein carbonylation detection

Communications Chemistry ◽

10.1038/s42004-021-00497-z ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Guillaume F. Combes ◽

Hussein Fakhouri ◽

Christophe Moulin ◽

Marion Girod ◽

Franck Bertorelle ◽

...

Keyword(s):

Optical Properties ◽

Contrast Agents ◽

Gold Nanoclusters ◽

Structural Features ◽

Optical Probe ◽

Protein Carbonyl ◽

Protein Carbonylation ◽

Post Translational Modification ◽

Post Translational Modifications ◽

Luminescent Probes

AbstractAtomically precise, ligand-protected gold nanoclusters (AuNCs) attract considerable attention as contrast agents in the biosensing field. However, the control of their optical properties and functionalization of surface ligands remain challenging. Here we report a strategy to tailor AuNCs for the precise detection of protein carbonylation—a causal biomarker of ageing. We produce Au15SG13 (SG for glutathione) with atomic precision and functionalize it with a thiolated aminooxy moiety to impart protein carbonyl-binding properties. Mass spectrometry and molecular modelling reveal the key structural features of Au15SG12-Aminooxy and its reactivity towards carbonyls. Finally, we demonstrate that Au15SG12-Aminooxy detects protein carbonylation in gel-based 1D electrophoresis by one- and two-photon excited fluorescence. Importantly, to our knowledge, this is the first application of an AuNC that detects a post-translational modification as a nonlinear optical probe. The significance of post-translational modifications in life sciences may open avenues for the use of Au15SG13 and other nanoclusters as contrast agents with tailored surface functionalization and optical properties.

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Electron microscopy and diffraction studies of polyimides

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100074069 ◽

1983 ◽

Vol 41 ◽

pp. 28-29

Author(s):

O.C. de Hodgins ◽

K. R. Lawless ◽

R. Anderson

Keyword(s):

Electron Microscopy ◽

Electron Microscope ◽

Structural Features ◽

Inert Atmosphere ◽

Polyimide Films ◽

Resolution Electron ◽

The Matrix ◽

High Resolution Electron Microscope ◽

Diffraction Patterns ◽

Polymeric Samples

Commercial polyimide films have shown to be homogeneous on a scale of 5 to 200 nm. The observation of Skybond (SKB) 705 and PI5878 was carried out by using a Philips 400, 120 KeV STEM. The objective was to elucidate the structural features of the polymeric samples. The specimens were spun and cured at stepped temperatures in an inert atmosphere and cooled slowly for eight hours. TEM micrographs showed heterogeneities (or nodular structures) generally on a scale of 100 nm for PI5878 and approximately 40 nm for SKB 705, present in large volume fractions of both specimens. See Figures 1 and 2. It is possible that the nodulus observed may be associated with surface effects and the structure of the polymers be regarded as random amorphous arrays. Diffraction patterns of the matrix and the nodular areas showed different amorphous ring patterns in both materials. The specimens were viewed in both bright and dark fields using a high resolution electron microscope which provided magnifications of 100,000X or more on the photographic plates if desired.

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