{"title":"Transcription factors and genome biases in polyploid crops.","authors":"Raminder Kaur, Vikas Rishi","doi":"10.1016/bs.apcsb.2024.09.005","DOIUrl":"10.1016/bs.apcsb.2024.09.005","url":null,"abstract":"<p><p>Nuclear protein transcription factors (TFs) regulate all biological processes in plants and are necessary for gene regulation. The transcription of genes during plant growth and development and their response to environmental cues are regulated by TF binding to specific promoter regions in the genomic DNA. Polyploid plants with several sets of chromosomes frequently display intricate genomic biases concerning TF expression. One or more subgenomes may dominate in terms of gene expression, leading to subgenome biases or dominance. These biases can influence various aspects of the crop's biology, including its growth, development, and adaptation. Advances in genomics have speed up the improvement of many important agricultural diploid crops, yet comparable endeavours in polyploid crops have been more challenging. This challenge primarily stems from the large size and intricate nature of the complex genome in polyploid crops, along with the need for comprehensive genome assembly data for such crop varieties as bread wheat, cotton and sugarcane. Several studies have evaluated the biased/asymmetric gene expression patterns, including TFs, within the polyploid crop genomes. In many polyploid crops, not all homologues of TF genes contribute equally to the phenotype. Here, we have examined polyploid crop plants for homeolog gene expression, emphasizing TFs. It is observed that the polyploids retain many gene alleles as functional homeologs that define important features involved in stress response, sugar metabolism, and fibre formation. The possible molecular mechanism describing the structural and epigenetic basis of differential subgenomic TF expression in polyploids is discussed.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"143 ","pages":"301-321"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Amar Jeet Yadav, Khushboo Bhagat, Akshit Sharma, Aditya K Padhi
{"title":"Navigating the landscape: A comprehensive overview of computational approaches in therapeutic antibody design and analysis.","authors":"Amar Jeet Yadav, Khushboo Bhagat, Akshit Sharma, Aditya K Padhi","doi":"10.1016/bs.apcsb.2024.10.011","DOIUrl":"10.1016/bs.apcsb.2024.10.011","url":null,"abstract":"<p><p>Immunotherapy, harnessing components like antibodies, cells, and cytokines, has become a cornerstone in treating diseases such as cancer and autoimmune disorders. Therapeutic antibodies, in particular, have transformed modern medicine, providing a targeted approach that destroys disease-causing cells while sparing healthy tissues, thereby reducing the side effects commonly associated with chemotherapy. Beyond oncology, these antibodies also hold promise in addressing chronic infections where conventional therapeutics may fall short. However, antibodies identified through in vivo or in vitro methods often require extensive engineering to enhance their therapeutic potential. This optimization process, aimed at improving affinity, specificity, and reducing immunogenicity, is both challenging and costly, often involving trade-offs between critical properties. Traditional methods of antibody development, such as hybridoma technology and display techniques, are resource-intensive and time-consuming. In contrast, computational approaches offer a faster, more efficient alternative, enabling the precise design and analysis of therapeutic antibodies. These methods include sequence and structural bioinformatics approaches, next-generation sequencing-based data mining, machine learning algorithms, systems biology, immuno-informatics, and integrative approaches. These approaches are advancing the field by providing new insights and enhancing the accuracy of antibody design and analysis. In conclusion, computational approaches are essential in the development of therapeutic antibodies, significantly improving the precision and speed of discovery, optimization, and validation. Integrating these methods with experimental approaches accelerates therapeutic antibody development, paving the way for innovative strategies and treatments for various diseases ranging from cancers to autoimmune and infectious diseases.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"144 ","pages":"33-76"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Host directed immunotherapy for chronic infections and cancer.","authors":"Rahul Tiwari, Vishal Kumar Singh, Vibhav Gautam, Sanjana Mehrotra, Rajiv Kumar","doi":"10.1016/bs.apcsb.2024.10.009","DOIUrl":"10.1016/bs.apcsb.2024.10.009","url":null,"abstract":"<p><p>Host-directed immunotherapy (HDI) is emerging as a transformative strategy in managing chronic diseases by leveraging the host's immune system to combat disease. This innovative approach has shown promise in a range of conditions, including cancer and parasitic infections. In oncology, HDI aims to enhance the body's natural immune response against cancer cells through mechanisms such as immune checkpoint inhibition, monoclonal antibodies, and cytokine therapies. These strategies are designed to boost the immune system's ability to recognize and destroy tumors, improving patient outcomes and offering alternatives to traditional cancer treatments. Similarly, in parasitic infections, HDI focuses on strengthening the host's immune defenses to control and eradicate those infections. For diseases like malaria, leishmaniasis, and Chagas disease, HDI strategies may involve adjuvants or immune modulators that amplify the body's ability to target and eliminate parasites. By optimizing immune responses and reducing reliance on conventional treatments, HDI holds the potential to revolutionize therapeutic approaches across various chronic diseases. This chapter highlights the flexibility and potential of HDI in advancing treatments, offering novel ways for improving patient care and disease management.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"144 ","pages":"355-388"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"From past to present: The evolution of immunotherapy and its modern modalities.","authors":"Surbhi Dadwal, Sarthak Dhar, Kirti Baghel, Amit Mishra, Sanjana Mehrotra, Vijay Kumar Prajapati","doi":"10.1016/bs.apcsb.2024.10.015","DOIUrl":"10.1016/bs.apcsb.2024.10.015","url":null,"abstract":"<p><p>Immunotherapy is emerging as a novel and reliable therapeutic technique for treating diseases such as autoimmunity, HIV/AIDS, allergy and cancers. This approach works by modulating the patient's immune system, activating both the innate and humoral branches to combat life-threatening diseases. The foundation of immunotherapy began with the discovery and development of \"serum therapy\" by German physiologist Emil Von Behring who received the Nobel Prize in 1901 for his contributions to the treatment of diphtheria. Around the same time, Dr. William Coley expanded the field for cancer treatment by developing the first immune based cure for sarcomas using attenuated strains of bacteria injected directly into patient's tumours. As medical science advanced, a broader understanding of the immune system and its components led to the emergence of different immunotherapeutic techniques. These include adoptive cell transfer therapy, cytokine therapy, cancer vaccines, and antibody-drug conjugates. The chapter provides a comprehensive understanding of the history and the current techniques used in immunotherapy, detailing the principles behind their mechanisms and the types of diseases tackled by each immunotherapeutic technique. By examining the journey from early discoveries to modern advancements, the chapter highlights the transformative impact of immunotherapy on medical science and patient care.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"144 ","pages":"1-32"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Nuclear transport protein suppresses Tau neurodegeneration.","authors":"Subashchandrabose Chinnathambi, Anusree Adithyan, Swathi Suresh, Gowshika Velmurugan, Madhura Chandrashekar, Surajita Sahu, Monalisa Mishra","doi":"10.1016/bs.apcsb.2024.07.001","DOIUrl":"10.1016/bs.apcsb.2024.07.001","url":null,"abstract":"<p><p>The nuclear pore complex, a large multimeric structure consists of numerous protein components, serves as a crucial gatekeeper for the transport of macromolecules across the nuclear envelope in eukaryotic cells. Dysfunction of the NPC has been implicated in various neurodegenerative diseases, including Alzheimer's disease. In AD, Tau aggregates interact with NPC proteins, known as nucleoporins, leading to disruptions in nuclear transport. Hyperphosphorylated Tau, a hallmark of AD pathology, interacts with central channel NUPs such as Nup62 and Nup98, causing cytoplasmic mis-localization of these proteins and impairing nuclear transport. Furthermore, Tau-NUP interactions promote Tau aggregation and the formation of neurofibrillary tangles, exacerbating neurodegeneration. Oligomeric Tau adheres to the lamin B receptor as well as nuclear lamin, preventing nucleocytoplasmic transport and resulting in heterochromatin unwinding, DNA damage, and neuronal death. The decrease in lamin B and increasing levels of lamin A along with C in AD-affected brain areas highlight the disease's intricacy. Furthermore, Tau internalization in the nucleus and interaction with nuclear pore complexes worsen NPC dysfunction, which contributes to neurotoxicity. Tau-DNA interactions suggest a chaperone-like role for Tau in DNA organization and repair, highlighting its involvement in maintaining genomic integrity. This review explores the intricate relationships between Tau, NPC components, and nuclear lamin in the context of AD, providing insights into the mechanisms underlying Tau-induced neurodegeneration and potential therapeutic targets.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"143 ","pages":"363-385"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Histone deacetylase's regulates Tau function in Alzheimer's disease.","authors":"Subashchandrabose Chinnathambi","doi":"10.1016/bs.apcsb.2024.09.008","DOIUrl":"10.1016/bs.apcsb.2024.09.008","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a prevalent neurodegenerative disease associated with dementia and neuronal impairments in brain. AD is characterized histopathologically by two hallmark lesions: abnormally phosphorylated Tau inside neurons as intracellular NFTs and extracellular accumulation of amyloid β peptide (Aβ). Furthermore, it is unable to clarify the distinction between the brief association between the development and build-up of Aβ and the commencement of illness. Additionally, a number of experimental findings suggest that symptoms related to Aβ may only manifest within the framework of anabatic Tauopathies. Tau, a natively unfolded protein, essentially involved in microtubule binding and assembly. Tau protein consists of truncated segment and the purpose of this truncated fragment is to initiate and promote the conversion of soluble Tau into aggregates. The most common aberrant posttranslational change found in Neuro Fibrillary Tangles is hyperphosphorylation, which is essentially composed of aggregated Tau. Tau phosphorylation and acetylation of Tau protein at the locations controlled by histone deacetylase 6 compete, which modulates Tau function. Considering the potential benefits of targeting HDAC6 in AD, we propose focusing on the role of HDAC6 in regulating Tau functions and the other targets are the therapeutic understanding of AD.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"143 ","pages":"339-361"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Nuclear podosomes regulates cellular migration in Tau and Alzheimer's disease.","authors":"Tazeen Qureshi, Madhura Chandrashekar, Vaishnavi Ananthanarayana, Murugappan Kumarappan, Nagaraj Rangappa, Gowshika Velmurugan, Subashchandrabose Chinnathambi","doi":"10.1016/bs.apcsb.2024.09.009","DOIUrl":"10.1016/bs.apcsb.2024.09.009","url":null,"abstract":"<p><p>The neuronal cytoskeleton has remained a less explored area of research in establishing neuroprotection. HDAC6 has been studied with respect to many neurodegenerative diseases, especially AD. It exhibits the ability to interact with various cytoskeletal proteins and to promote migration in cells. Podosomes are actin microstructures that help cells to migrate in the extracellular environment. The aim of this review is to bring into focus the significance of studies on the involvement of podosomes in Alzheimer's disease. We have suggested that Histone Deacetylase 6 plays a vital role in AD, through its interactions with the various signalling processes in the cell, most importantly the cytoskeletal remodelling machinery within the podosomes.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"143 ","pages":"411-426"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Revolutionizing pancreatic cancer treatment with CAR-T therapy.","authors":"Kirti Baghel, Sanjana Mehrotra, Vijay Kumar Prajapati","doi":"10.1016/bs.apcsb.2024.10.008","DOIUrl":"10.1016/bs.apcsb.2024.10.008","url":null,"abstract":"<p><p>Pancreatic cancer remains one of the most lethal malignancies, with a five-year survival rate among the lowest of all cancers. This poor prognosis is largely due to the aggressive nature of the disease and its resistance to conventional treatments such as surgery, chemotherapy, and radiation therapy. Chimeric antigen receptor (CAR) T-cell therapy, a novel immunotherapeutic approach leverages the patient's own immune system to specifically target and eliminate cancer cells by genetically engineering T cells to express CARs that recognize tumor-specific antigens. While CAR-T therapy has demonstrated remarkable success in treating hematologic malignancies, its application to solid tumors like pancreatic cancer presents significant challenges. Recent advancements in CAR-T cell design, like the addition of co-stimulatory domains and dual-targeting CARs, have enhanced their efficacy against solid tumors. Additionally, strategies to modify the tumor microenvironment (TME), such as combining CAR-T therapy with immune checkpoint inhibitors and cytokine modulation, are being investigated to boost CAR-T cell activity against pancreatic cancer. Early-phase clinical trials targeting antigens such as carcinoembryonic antigen (CEA) and mesothelin (MSLN) in pancreatic cancer have yielded encouraging results, though obstacles like antigen escape and limited T-cell persistence remain significant challenges. This chapter outlines the current state of CAR-T therapy for pancreatic cancer, focusing on the emerging approaches to address these obstacles and underscore the potential of CAR-T therapy to transform the future of pancreatic cancer treatment.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"144 ","pages":"331-353"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sergei Y Grishin, Alexey K Surin, Oxana V Galzitskaya
{"title":"Investigation of new non-toxic inhibitors of fibril formation and preservatives for insulin preparations its analogues.","authors":"Sergei Y Grishin, Alexey K Surin, Oxana V Galzitskaya","doi":"10.1016/bs.apcsb.2024.09.013","DOIUrl":"https://doi.org/10.1016/bs.apcsb.2024.09.013","url":null,"abstract":"<p><p>Insulin and its analogue formulations are the main components in the therapy of insulin-dependent forms of diabetes. Insulin and its analogues can form amyloid-like aggregates during long-term storage and local concentration increases, leading to reduced therapeutic efficacy and potential side effects such as insulin amyloidosis. The aim of this study was to identify and propose new non-toxic inhibitors and preservatives to replace phenol in insulin formulations. The peptide FVNQH and phenol red were studied as promising inhibitors of fibril formation of insulin, lispro, and glargine in vitro using the specific amyloid dye thioflavin T. The peptide FVNQH and phenol red (0.5-1 mg/mL) showed a bacteriostatic effect on the E. coli K-12 strain after 24 h. The fibril-inhibiting and antimicrobial effects of these substances were similar to the effect of phenol at a concentration of 0.5 mg/mL. Thus, the identified inhibitors can potentially replace phenolic components in slowing amyloid aggregation and increase the stability of insulin and its analogues.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"145 ","pages":"113-143"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Guilherme C de Andrade, Michelle F Mota, Dinarte N Moreira-Ferreira, Jerson L Silva, Guilherme A P de Oliveira, Mayra A Marques
{"title":"Protein aggregation in health and disease: A looking glass of two faces.","authors":"Guilherme C de Andrade, Michelle F Mota, Dinarte N Moreira-Ferreira, Jerson L Silva, Guilherme A P de Oliveira, Mayra A Marques","doi":"10.1016/bs.apcsb.2024.09.010","DOIUrl":"https://doi.org/10.1016/bs.apcsb.2024.09.010","url":null,"abstract":"<p><p>Protein molecules organize into an intricate alphabet of twenty amino acids and five architecture levels. The jargon \"one structure, one functionality\" has been challenged, considering the amount of intrinsically disordered proteins in the human genome and the requirements of hierarchical hetero- and homo-protein complexes in cell signaling. The assembly of large protein structures in health and disease is now viewed through the lens of phase separation and transition phenomena. What drives protein misfolding and aggregation? Or, more fundamentally, what hinders proteins from maintaining their native conformations, pushing them toward aggregation? Here, we explore the principles of protein folding, phase separation, and aggregation, which hinge on crucial events such as the reorganization of solvents, the chemical properties of amino acids, and their interactions with the environment. We focus on the dynamic shifts between functional and dysfunctional states of proteins and the conditions that promote protein misfolding, often leading to disease. By exploring these processes, we highlight potential therapeutic avenues to manage protein aggregation and reduce its harmful impacts on health.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"145 ","pages":"145-217"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}