Advances in protein chemistry and structural biology最新文献

{"title":"Tau proteotasis in Alzheimer's disease.","authors":"Subashchandrabose Chinnathambi","doi":"10.1016/bs.apcsb.2024.09.003","DOIUrl":"https://doi.org/10.1016/bs.apcsb.2024.09.003","url":null,"abstract":"<p><p>Tau protein accumulation is one of the characteristic features of Alzheimer's disease (AD). Their accumulation is driven by the formation of intermediate toxic oligomers of Tau to the highly ordered neurofibrillary tangles. Cellular machineries engage different types of proteins such as, chaperone-co-chaperones complex, ubiquitin, kinases, proteases etc., to clear the aberrantly accumulated Tau protein which otherwise would cause neuronal death. In the milieu of proteotoxicity, it would be significant for the cell to follow a specific path for Tau clearance. Under this circumstance, cells express key proteins and other accessory proteins specific to the pathway. This is known to be dependent on the post-translational modifications and mutations associated with Tau. The processes involved maintenance of proteins homeostasis in cells collectively called proteostasis. The proteostasis involve the synthesis of proteins by ribosomes, protein folding mostly by chaperons and the degradation of improperly folded or unwanted proteins. Autophagy is the mechanism to eradicate unwanted, non-functional and toxic proteins from the cell. Proteostasis plays a pivotal role in maintaining the normal cellular environment in the expense of considerable amount of energy. AD is the prevalent type of dementia associated with aging, which is characterized by aggregation of Tau.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"147 ","pages":"333-353"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145090866","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":"Exploring immunotherapy to control human infectious diseases.","authors":"Praveen Rai, Sanjana Mehrotra, Vijay Kumar Prajapati","doi":"10.1016/bs.apcsb.2024.10.010","DOIUrl":"10.1016/bs.apcsb.2024.10.010","url":null,"abstract":"<p><p>Infectious diseases continue to pose significant challenges to global health, especially with the rise of antibiotic resistance and emerging pathogens. Traditional treatments, while effective, are often limited in the face of rapidly evolving pathogens. Immunotherapy, which harnesses and enhances the body's immune response, offers a promising alternative to conventional approaches for the treatment of infectious diseases. By employing use of monoclonal antibodies, vaccines, cytokine therapies, and immune checkpoint inhibitors, immunotherapy has demonstrated considerable potential in overcoming treatment resistance and improving patient outcomes. Key innovations, including the development of mRNA vaccines, use of immune modulators, adoptive cell transfer, and chimeric antigen receptor (CAR)-T cell therapy are paving the way for more targeted pathogen clearance. Further, combining immunotherapy with conventional antibiotic treatment has demonstrated effectiveness against drug-resistant strains, but this chapter explores the evolving field of immunotherapy for the treatment of bacterial, viral, fungal, and parasitic infections. The chapter also explores the recent breakthroughs and ongoing clinical trials in infectious disease immunotherapy.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"144 ","pages":"389-429"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466726","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":"Role of protein aggregates in bacteria.","authors":"Ewa Laskowska, Dorota Kuczyńska-Wiśnik, Karolina Stojowska-Swędrzyńska","doi":"10.1016/bs.apcsb.2024.09.012","DOIUrl":"https://doi.org/10.1016/bs.apcsb.2024.09.012","url":null,"abstract":"<p><p>Protein misfolding and aggregation in bacteria, induced by a variety of intrinsic and environmental stresses, have often been associated with proteostasis disruption and toxic effects. However, a growing body of evidence suggests that these aggregates may also serve as functional membrane-less organelles (MLOs), playing a protective role in bacterial cells. The main mechanism responsible for the formation of MLOs is liquid-liquid phase separation (LLPS), a process that transforms a homogenous solution of macromolecules into dense condensates (liquid droplets) and a diluted phase. Over time, these liquid droplets can be transformed into solid aggregates. Bacterial MLOs, containing one dominant component or hundreds of cytoplasmic proteins, have been shown to be involved in various processes, including replication, transcription, cell division, and stress tolerance. The protective function of bacterial MLOs involves sequestration and protection of proteins and RNA from irreversible inactivation or degradation, upregulation of molecular chaperones, and induction of a dormant state. This protective role is particularly significant in the case of pathogenic bacteria exposed to antibiotic therapy. In a dormant state triggered by protein aggregation, pathogens can survive antibiotic therapy as persisters and, after resuming growth, can cause recurrent infections. Recent research has explored the potential use of bacterial MLOs as nanoreactors that catalyze biochemical reactions or serve as protein reservoirs and biosensors, highlighting their potential in biotechnology.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"145 ","pages":"73-112"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958311","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":"Preface.","authors":"Dr Vijay Kumar Prajapati","doi":"10.1016/S1876-1623(25)00019-7","DOIUrl":"https://doi.org/10.1016/S1876-1623(25)00019-7","url":null,"abstract":"","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"144 ","pages":"xix"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466654","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":"Immunotherapy in the management of inflammatory bone loss in osteoporosis.","authors":"Leena Sapra, Rupesh K Srivastava","doi":"10.1016/bs.apcsb.2024.10.013","DOIUrl":"10.1016/bs.apcsb.2024.10.013","url":null,"abstract":"<p><p>Osteoporosis, a progressive skeletal disorder characterized by decreased bone mass and increased fracture risk, has traditionally been treated with pharmacological agents targeting bone remodeling. However, emerging research highlights the critical role of immune system in regulating bone metabolism, introducing the concept of Osteoimmunology. Chronic low-grade inflammation is now recognized as a significant contributor to osteoporosis, particularly in postmenopausal women and the elderly. Immune cells, such as T cells and B cells, and their secreted cytokines directly influence bone resorption and formation, tipping the balance toward net bone loss in inflammatory environments. Immunotherapy, a treatment modality traditionally associated with cancer and autoimmune diseases, is now gaining attention in the management of osteoporosis. By targeting immune dysregulation and reducing inflammatory bone loss, immunotherapies offer a novel approach to treating osteoporosis that goes beyond merely inhibiting bone resorption or promoting bone formation. This therapeutic strategy includes monoclonal antibodies targeting inflammatory cytokines, cell-based therapies to enhance the function of regulatory T and B cells, and interventions aimed at modulating immune pathways linked to bone health. This chapter reviews the emerging role of immunotherapy in addressing inflammatory bone loss in osteoporosis. Present chapter also explores the underlying immune mechanisms contributing to bone degradation, current immunotherapeutic strategies under investigation, and the potential of these approaches to revolutionize the management of osteoporosis.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"144 ","pages":"461-491"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466747","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":"Role of lamins in cellular physiology and cancer.","authors":"Ravi Chauhan, Ashna Gupta, Gunjan Dagar, Shalini Sharma, Hana Q Sadida, Sheema Hashem, Ann M Verghese, Mukesh Tanwar, Muzafar A Macha, Shahab Uddin, Ammira S Al-Shabeeb Akil, Tej K Pandita, Ajaz A Bhat, Mayank Singh","doi":"10.1016/bs.apcsb.2024.06.002","DOIUrl":"10.1016/bs.apcsb.2024.06.002","url":null,"abstract":"<p><p>Lamins, which are crucial type V intermediate filament proteins found in the nuclear lamina, are essential for maintaining the stability and function of the nucleus in higher vertebrates. They are classified into A- and B-types, and their distinct expression patterns contribute to cellular survival, development, and functionality. Lamins emerged during the transition from open to closed mitosis, with their complexity increasing alongside organism evolution. Derived from the LMNA, LMNB1, and LMNB2 genes, lamins undergo alternative splicing to produce seven variants, influencing cellular processes such as stiffness, chromatin condensation, and cell cycle regulation. The lamin network interacts with the cytoskeleton via Linkers of the nucleoskeleton to the cytoskeleton (LINC) complexes, playing a critical role in cellular stability and mechanotransduction. Lamins also regulate active transport into and out of the nucleus, affecting nuclear integrity, positioning, DNA maintenance, and gene expression. Genetic mutations in lamin genes lead to laminopathies, highlighting their functional significance and organizational roles. Changes in lamin subtype composition within the nuclear lamina have significant implications for cancer development, impacting cellular stiffness, mobility, and the Epithelial-to-Mesenchymal Transition (EMT). Lamin A/C, in particular, plays multifaceted roles in cancer biology, influencing progression, metastasis, and therapy response through interactions with various proteins and pathways. Dysregulated lamin expression is commonly observed in cancers, suggesting their potential as diagnostic and prognostic markers. This chapter underscores the pivotal roles of lamins in nuclear architecture and cancer biology, emphasizing their impact on cellular functions and disease pathology. Understanding lamin behavior and regulation mechanisms holds promise for developing novel diagnostic tools and targeted therapies in cancer treatment.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"143 ","pages":"119-153"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021808","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 infection to remedy: Harnessing oncolytic viruses in cancer treatment.","authors":"Sramona Kar, Sanjana Mehrotra, Vijay Kumar Prajapati","doi":"10.1016/bs.apcsb.2024.10.012","DOIUrl":"10.1016/bs.apcsb.2024.10.012","url":null,"abstract":"<p><p>Oncolytic virus (OV) mediated immunotherapy is one of the recent techniques used to treat higher grade cancers where conventional therapies like chemotherapy, radiation fail. OVs as a therapeutic tool show high efficacy and fewer side effects than conventional methods as supported by multiple preclinical and clinical studies since they are engineered to target tumours. In this chapter, we discuss the modifications in viruses to make them oncolytic, types of strains commonly administered, mechanisms employed by viruses to specifically target and eradicate malignancy and progress achieved as reported in case studies (preclinical and clinical trials). OVs also face some unique challenges with respect to the malignancy being treated and the varied pathogen exposure of the patients, which is also highlighted here. Since pathogen exposure varies according to population dynamics worldwide, chances of generating a non-specific recall response to an OV cannot be negated. Lastly, the future perspectives and ongoing practises of combination therapies are discussed as they provide a leading edge over monotherapies in terms of tumour clearance, blocking metastasis and enhancing patient survival. Efforts undertaken to overcome current challenges are also highlighted.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"144 ","pages":"213-257"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466737","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":"Protein structure prediction with evolutionary algorithm.","authors":"Rafael Stubs Parpinelli, Nicholas Wojeicchowski, Nilcimar Neitzel Will","doi":"10.1016/bs.apcsb.2024.09.006","DOIUrl":"10.1016/bs.apcsb.2024.09.006","url":null,"abstract":"<p><p>Three-dimensional protein structure prediction is one of the fundamental problems of Structural Bioinformatics. The use of problem information through fragment insertion, secondary structure, and contact maps can help explore the search space better. An evolutionary algorithm is proposed in this work, which uses this problem information for protein structure prediction. In the proposed method, a dynamic speciation technique and fragment insertion are used to promote the diversity of the population. The fragment library is generated based on the Rosetta Quota protocol to provide fragments with increased diversity. The information from contact maps and secondary structure are used in two selection strategies to better explore the conformational search space. The results of an experiment with nine proteins are presented. Results obtained are competitive with the literature and are compared in terms of RMSD, GDT, and processing time.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"147 ","pages":"101-127"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145090792","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":"Deciphering the impact of ABCA4 genetic variants of unknown significance in inherited retinal disease through computational and functional approaches.","authors":"Senem Cevik, Jazzlyn S Jones, Subhasis B Biswas, Esther E Biswas-Fiss","doi":"10.1016/bs.apcsb.2024.12.003","DOIUrl":"https://doi.org/10.1016/bs.apcsb.2024.12.003","url":null,"abstract":"<p><p>Variants in the ABCA4 gene are a fundamental cause of several inherited retinal degenerations (IRDs), including Stargardt macular dystrophy, retinitis pigmentosa, and cone-rod dystrophy. These three ABCA4-driven diseases are estimated to cause blindness in 1.4 million people worldwide. As a result, genetic testing of ABCA4 is increasingly common in clinical settings. Of the 4111 identified variants in ABCA4, 1668 are missense, of which 47 % are of unknown pathogenicity (variants of unknown significance, VUS). This genetic uncertainty leads to three fundamental problems: (i) for IRD patients with multiple unclassified ABCA4 mutations, it is impossible to predict which variant will cause disease in relatives who have not yet developed it; (ii) development of variant-specific therapies remains limited; and (iii) these variants cannot be used to predict disease prospectively, which is essential for life-planning decisions and for directing patients to new clinical trials. This chapter describes approaches to deciphering the impact of ABCA4 genetic variants of unknown significance (VUS) using a combination of in silico and in vitro analyses. By leveraging complementary fields-protein biochemistry and computational biology-to create a \"sequence-structure-function\" workflow, where in silico 3D protein structural analysis of ABCA4 sequence variants serves as a tool to predict disease severity and clinical pathogenicity in conjunction with first-line bioinformatic tools and functional analysis. This approach represents a helpful step forward in understanding how ABCA4 variants affect structure and function and in evaluating their potential to cause inherited retinal diseases.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"147 ","pages":"423-460"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145090742","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":"Tau protein structure and dynamics.","authors":"Subashchandrabose Chinnathambi, Gowshika Velmurugan, Madhura Chandrashekar","doi":"10.1016/bs.apcsb.2024.09.002","DOIUrl":"https://doi.org/10.1016/bs.apcsb.2024.09.002","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is the most common type of dementia. It is characterized by chronic memory defects, alterations in behavior, and cognitive decline. AD is histopathologically characterized by two hallmarks: intracellular accumulation of Tau protein as neurofibrillary tangles (NFTs) and extracellular deposition of amyloid beta. In this book chapter, we highlighted the microtubule-associated protein Tau, exploring its structural diversity and its distinct isoforms. It is an intrinsically disordered protein which lacks three-dimensional structure that are defined by their vast structural segments that undergo rapid and prolonged conformational alterations. It has not been possible to analyze the structure of disordered proteins since they often have different conformations and are very flexible. Tau proteins comprise various domains that significantly participate in physiology in neurons, including stabilizing microtubule structure and dynamics and axonal cargo transport. In its physiological state, Tau interacts with various molecules and proteins. By various post-translational modifications at specific sites in Tau protein, including phosphorylation, acetylation, and methylation. Tau protein undergo pathological structural confirmation by hyperphosphorylation, forming insoluble oligomers, and developing as paired helical filaments. Finally, as the disease progressed, it accumulated inside the neurons as NFTs.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"147 ","pages":"241-258"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145090874","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}