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- Volume 31, Issue 10, 2024
Protein and Peptide Letters - Volume 31, Issue 10, 2024
Volume 31, Issue 10, 2024
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The Present State and Impact of AI-Driven Computational Tools for Predicting Plant Protein Structures
Authors: Stanislaus Antony Ceasar and Heba Talat EbeedSeveral key functions of plants, such as photosynthesis, nutrient transport, disease resistance, and abiotic tolerance, are manifested by several classes of proteins. Prediction of 3-dimensional (3-D) structures of proteins and their working mechanisms can have a profound impact on plant proteomics research and could help improve key agricultural traits in crop plants. This review aims to present the current status of plant protein structure determination and discuss the way forward. Most experimentally proven protein structures are available only for the model plant Arabidopsis thaliana. Most of the key crop plants have only a few hundred or fewer experimentally proven 3-D structures. Fewer than 1% of the protein sequences in the majority of plants have had their 3D structures experimentally determined, and A. thaliana is the sole plant with the highest percentage of 1.4% of protein sequences with experimentally determined structures. AI-based protein structure prediction tool AlphaFold has predicted models of several thousand proteins for many crop plants. In AlphaFold predicted protein models, soybean has the highest percentage (65%) of its UniProt protein sequences with predicted models, and a few other crop plants have also a considerable percentage of its UniProt sequences with AlphaFold predicted models. AlphaFold might help predict models and bridge the gap in plant structure determination studies. Protein structure information might lead to engineering key residues to improve the agronomical performance of crop plants.
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Ferroptosis as a Therapeutic Target in Neurodegenerative Diseases: Exploring the Mechanisms and Potential of Treating Alzheimer's Disease and Parkinson's Disease
Authors: Hui Zhong, Hanxiang Liu and Qiang FuAmidst the rising global burden of neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases, there is an urgent need for novel therapeutic strategies to combat these debilitating conditions. These diseases are characterized by progressive neural dysfunction leading to cognitive impairments, for which current therapeutic strategies remain palliative at best. Recently, the discovery of ferroptosis, a novel cell death mode that is different from apoptosis and autophagy, has opened new avenues in the field of cognitive research. With in-depth research on ferroptosis, the clinical significance of iron homeostasis disorders and lipid peroxidation in the occurrence, development, and treatment of neurodegenerative diseases are gradually becoming apparent. This study aims to elucidate the roles of ferroptosis in the context of neurodegeneration and to explore its potential as a therapeutic target. By unraveling the intricate relationship between iron homeostasis disorders, oxidative damage, and lipid metabolism disturbances in these diseases, new intervention targets are revealed. It offers a new dimension to the management of neurocognitive impairments in Alzheimer's and Parkinson's diseases. The implications of these findings extend beyond just Alzheimer's and Parkinson's diseases. They also have relevance with other neurological conditions characterized by oxidative stress and iron dysregulation. This review contributes to increased knowledge of ferroptosis and provides a foundational understanding that could lead to the development of innovative therapeutic strategies. Ultimately, it may alleviate the development of neurodegenerative diseases and improve cognitive function by preventing ferroptosis, which has not only academic significance but also potential clinical significance.
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Immunoproteomics: Approach to Diagnostic and Vaccine Development
The study of large protein sets (proteomics) involved in the immunological reaction is known as immunoproteomics. The methodology of immunoproteomics plays a major role in identifying possible vaccine candidates that could protect against pathogenic infection. The study of immunogenic proteins that are expressed during the outset of infection is the focus of the cross-talk between proteomics and immune protection antigens utilizing serum. Peptide presentation by MHC provides the new ‘window’ into changes that occur in the cell. Thus, there is strong, intense pressure on the pathogen that has been mutated in such an unusual manner that it can bypass the MHC peptide presentation by the MHC molecule. The pathogen's ability to evade the immune system is strongly restricted by the two unique distinct properties of MHC molecules, i.e., polygenic and polymorphic properties. MHC-I restriction epitope identification has traditionally been accomplished using genetic motif prediction. The study of immune system proteins and their interactions is the main emphasis of the specialist field of immunoproteomics within proteomics. Methodologies include mass spectrometry (MS), SRM assay, MALDI-TOF, Chromatography, ELISA, 2DG PAGE, and bioinformatics tools. Challenges are the complexity of the immune system, protein abundance and dynamics, sample variability, post-translational modifications (PTMs), and data integration. Current advancements are enhanced mass spectrometry techniques, single-cell proteomics, artificial intelligence and machine learning, advanced protein labeling techniques, integration with other omics technologies, and functional proteomics. However, the recently emerging field of immunoproteomics has more promising possibilities in the field of peptide-based vaccines and virus-like particle vaccines. The importance of immunoproteomics technologies and methodologies, as well as their use in the field of vaccinomics, are the main topics of this review. Here, we have discussed immunoproteomics in relation to a step towards the future of vaccination.
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Honeybee Venom: A Potential Source of Anticancer Components
Cancer is a deadly disease that has claimed millions of lives worldwide. Traditional cancer treatments, such as chemotherapy and radiation, have been used for many years but have become less favored due to drug resistance, lack of tumor selectivity, high costs, and various side effects, such as fatigue and hair loss. Many studies have reported that animal venoms, such as those from snakes, scorpions, and bees, contain bioactive peptides that can be synthesized into anti-cancer peptides (ACPs), which offer a potential alternative to traditional cancer therapies. Apitherapy is an area of growing interest for the development of new cancer treatments using bee venom, which is a complex mixture of biologically active peptides, enzymes, bioactive amines, and non-peptide components that have been found to have anti-cancer properties. By leveraging these bioactive peptides, researchers could develop ACPs that are more targeted towards cancer cells, reducing the risk of adverse side effects and improving patient outcomes. The use of bee venom components in targeting cancer could provide a more selective, effective, and affordable approach to cancer therapy. While further research is needed, the potential benefits of using bee venom components in cancer therapy are significant and could help improve the lives of cancer patients worldwide. This study aims to review the components of bee venom as potential cancer treatments.
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Characterization of Luciferase from Photorhabdus kayaii and its Application for In vivo Imaging Studies in Mice
BackgroundBioluminescence, or the production of light by luciferases, is the basis of a well-known reporter technology. A quick way to study the efficacy of antimicrobial drugs and vaccines is in vivo bioluminescence imaging (BLI). Photorhabdus spp. represent the only terrestrial group of bioluminescent bacteria. The luciferase obtained from Photorhabdus luminescence has been widely used in BLI studies. However, little information is available about the functions of luciferases obtained from other members of this genera.
ObjectiveThis study aimed to evaluate the applicability of the luciferase obtained from Photorhabdus kayaii for BLI studies.
MethodsP. kayaii starE, an Iranian isolate of P. kayaii, was cultivated on NBTA agar plates. The resulting colonies were cultured on McConkey agar to determine the bacterial phase. Bioluminescence emission was measured using a multimode reader. The luciferase genes of this bacterium were sequenced following the PCR amplification, and the corresponding amino acid sequences were determined. The luciferase tertiary structure was then obtained from the TACOS web server and compared to that of P. luminescence in CE software. The lux operon encoding the luciferase (luxA and luxB genes) and substrate synthesis complex was cloned and expressed in Escherichia coli BL21 (DE3) using the pBBR1MCS2_START vector. The luminescence emission during the growth was examined. Moreover, the effects of pH and sodium deoxycholate (bile salt) on bioluminescence emission were investigated. Appropriate conditions for the use of bioluminescent E. coli for BLI studies in mice were demonstrated in terms of cell numbers and injection routes.
ResultsThe bacterium was luminescent and in phase I. Its luciferase monomers (α and β) shared 100% amino acid homology with P. kayaii M-HU2 and more than 92% with P. luminescence. Tertiary structures of the luciferase monomers were 93%- 95% identical to those of P. luminescence. The lux operon was expressed in E. coli, and the maximum bioluminescence signal was observed during the decelerating phase of growth. The bioluminescence at different pH values correlated with the cell survival. The luminescence was emitted by cells exposed to the bile salt. A strong bioluminescent signal was emitted from mice after subcutaneous injection of bioluminescent E. coli at 107 CFU. However, no signals were emitted from mice that were administered the same cell number via intraperitoneal injection. A 2.5-fold increase in the cell number resulted in bioluminescence detection in the abdomen of mice after intraperitoneal injection and a 3.22-fold increase in signal intensity after subcutaneous injection.
ConclusionThese results demonstrated the usefulness of P. kayaii luciferase for BLI studies.
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Comparative Analysis of IMT-P8 and LDP12 Cell-Penetrating Peptides in Increasing Immunostimulatory Properties of HIV-1 Nef-MPER-V3 Antigen
BackgroundThere have been great efforts in vaccine design against HIV-1 since 1981. Various approaches have been investigated, including optimized delivery systems and effective adjuvants to enhance the efficacy of selective antigen targets. In this study, we evaluated the efficiency of IMT-P8 and LDP12 cell penetrating peptides in eliciting immune responses against HIV-1 Nef-MPER-V3 fusion protein as an antigen candidate. Moreover, the potency of HP91 and HSP27 was compared as an adjuvant in female BALB/c mice through different regimens.
MethodsFor this purpose, the recombinant Nef-MPER-V3, IMT-P8-Nef-MPER-V3 and LDP-Nef-MPER-V3 proteins were generated on a large scale. After mice immunization with different regimens, the secretion of antibodies, cytokines and granzyme B was evaluated by ELISA.
ResultsOur results demonstrated that immunized mice receiving the Nef-MPER-V3 linked to IMT-P8 exhibited significantly higher levels of IgG compared to other groups. The IMT-P8-Nef-MPER-V3 with the Hp91 group showed the highest level of humoral response, which was significantly stronger than the LDP12 formulation using the same antigen (LDP-Nef-MPER-V3). Additionally, the combination of IMT-P8-Nef-MPER-V3 with either Hp91 or Hsp27 resulted in robust induction of IFN-γ compared to the LDP-Nef-MPER-V3 group. Furthermore, cytotoxic T lymphocyte (CTL) activation and proliferation assays indicated that IMT-P8 served as a more effective CPP, particularly when used in conjunction with the Hp91 adjuvant.
ConclusionAltogether, the data indicated that Nef-MPER-V3 antigen in different formulations was effective in eliciting immune responses. This fusion protein has the high potency to induce both immunity arms, specifically when incorporated with IMT-P8, which showed priority to LDP12. Moreover, HP91 resulted in a greater humoral and cellular immune activation compared to HSP27. These findings suggest the potential of IMT-P8 as a superior delivery system for enhancing immune responses in vaccine development.
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Volumes & issues
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Volume 31 (2024)
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Volume 30 (2023)
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Volume 29 (2022)
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Volume 28 (2021)
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Volume 27 (2020)
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Volume 26 (2019)
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Volume 25 (2018)
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Volume 24 (2017)
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Volume 23 (2016)
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Volume 22 (2015)
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Volume 21 (2014)
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Volume 20 (2013)
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Volume 19 (2012)
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Volume 18 (2011)
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Volume 17 (2010)
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Volume 16 (2009)
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Volume 15 (2008)
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Volume 14 (2007)
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Volume 13 (2006)
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Volume 12 (2005)
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Volume 11 (2004)
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Volume 10 (2003)
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Volume 9 (2002)
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Volume 8 (2001)