{"title":"Structure of the Myosin Thick Filaments in Muscle.","authors":"Pradeep K Luther","doi":"10.1007/978-3-032-05273-5_2","DOIUrl":"10.1007/978-3-032-05273-5_2","url":null,"abstract":"<p><p>Striated muscle is composed of overlapping arrays of thick myosin filaments and thin actin filaments. The thick filaments are composed of myosin molecules, which are hexamers of two heavy chains and two pairs of light chains. The heavy chain has an N-terminal head domain and a C-terminal helical rod domain. The latter dimerises to form a two-stranded coiled-coil rod. The distal two-thirds of these rods aggregate in parallel to form the filament backbone, while the heads lie on the surface to facilitate interactions with actin. The molecules aggregate in an antiparallel manner in the centre of the A-band to form the so-called bare zone. The proximal one-third of the rod can swivel and thereby allow the myosin heads to interact with actin. The atomic structure of the head, determined in the 1990s, was a major milestone in the muscle field. Over the next three decades, great strides were made in cryo-electron microscope technology and software. This led to the high-resolution structure of the insect flight muscle thick filament, showing the structure of the myosin tails at 6 Å resolution and the structure of the heads. There has been great excitement recently with the high-resolution structures of relaxed cardiac muscle thick filaments showing details of all the important players: three types of myosin crowns and the paths of their tails, the structure and interactions of cMyBP-C and the structure of two unique forms of titin and its role in filament assembly. Hypertrophic cardiomyopathy, which results from mutations in sarcomeric proteins, especially myosin and cMyBP-C, is a major health burden and insight gained from the new studies will help to devise new therapies.</p>","PeriodicalId":21991,"journal":{"name":"Sub-cellular biochemistry","volume":"113 ","pages":"35-58"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146011858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Claudiu T Supuran, Rashmi Pundeer, Clemente Capasso
{"title":"Industrial and Environmental Applications of Carbonic Anhydrases.","authors":"Claudiu T Supuran, Rashmi Pundeer, Clemente Capasso","doi":"10.1007/978-3-032-23172-7_9","DOIUrl":"10.1007/978-3-032-23172-7_9","url":null,"abstract":"<p><p>Carbonic anhydrases (CAs) are highly efficient metalloenzymes catalyzing the reversible conversion of carbon dioxide (CO<sub>2</sub>) into bicarbonate (HCO<sub>3</sub><sup>-</sup>) and protons (H<sup>+</sup>). Over the past decades, CAs have been employed across diverse industrial and environmental applications, including carbon management and CO<sub>2</sub> capture, chemical synthesis, biomineralization, water treatment, and renewable energy generation. This chapter provides a comprehensive overview of CA-based technologies, emphasizing their transition from laboratory research to pilot- and industrial-scale applications. Key topics covered include enzyme-assisted CO<sub>2</sub> absorption, reactor and solvent design, enzyme immobilization, and hybrid systems integrating chemical, biological, or electrochemical conversion. The chapter also examines operational challenges, mitigation strategies, and future perspectives, highlighting how CAs can enable sustainable, low-energy, and value-added processes. It illustrates the integration of mechanistic insights, process design, and real-world examples, providing a valuable resource for both researchers and industrial practitioners.</p>","PeriodicalId":21991,"journal":{"name":"Sub-cellular biochemistry","volume":"123 ","pages":"179-194"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147821180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Carbonic Anhydrase Inhibitors in Oncology.","authors":"Claudiu T Supuran, Andrea Angeli","doi":"10.1007/978-3-032-23172-7_6","DOIUrl":"10.1007/978-3-032-23172-7_6","url":null,"abstract":"<p><p>Tumor hypoxia and extracellular acidosis are hallmarks of the tumor microenvironment that promote cancer progression, metabolic adaptation, and resistance to therapy. Among the molecular mediators of these processes, carbonic anhydrase IX (CA IX) and carbonic anhydrase XII (CA XII) play central roles in maintaining intracellular pH homeostasis and facilitating tumor cell survival under hypoxic stress, making them highly attractive targets for selective therapeutic intervention. This has prompted an effort to inhibit specific CA isoforms, as an anticancer therapeutic strategy with small molecule inhibitors, one of which (SLC-0111) completed Phase I clinical trials. However, other CA isoforms also show similar activity and tissue distribution in cancers and have not been considered as therapeutic targets for cancer treatment. Recent findings have revealed that CA IX and CA XII are not only critical for pH regulation but also intersect with key metabolic and redox pathways, including ferroptosis, glutathione metabolism, and mitochondrial iron-sulfur cluster biogenesis. Parallel advances in drug design have expanded this therapeutic paradigm through the development of dual-target inhibitors, combining CA IX/XII inhibition with modulation of other cancer-associated pathways. Beyond small-molecule inhibitors, antibody-based approaches have reached clinical and preclinical development as imaging agents, radioimmunotherapeutics, antibody-drug conjugates, and nanomaterial conjugates. Collectively, these strategies highlight the potential of exploiting the metabolic vulnerabilities of hypoxic tumors by co-targeting CA IX/XII with complementary redox or survival pathways, paving the way toward rational polypharmacology in precision oncology.</p>","PeriodicalId":21991,"journal":{"name":"Sub-cellular biochemistry","volume":"123 ","pages":"101-146"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147821081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"COG Complex in Golgi Trafficking and Glycosylation.","authors":"Farhana Taher Sumya, Vladimir V Lupashin","doi":"10.1007/978-3-032-16833-7_7","DOIUrl":"10.1007/978-3-032-16833-7_7","url":null,"abstract":"<p><p>The Conserved Oligomeric Golgi (COG) complex, an evolutionary conserved octameric vesicular tether, is essential for maintaining Golgi function by ensuring accurate delivery of resident proteins to their specific locations. Mutations in human COG subunits result in severe multi-systemic diseases known as COG-Congenital Disorders of Glycosylation (COG-CDG). This review explores the current knowledge of COG complex structure, its dynamic behavior, interactions with partner proteins, and proposed models of its cellular functions. Furthermore, we will discuss the pathological implications of mutations in COG complex subunits, as observed in model organisms and human patients.</p>","PeriodicalId":21991,"journal":{"name":"Sub-cellular biochemistry","volume":"111 ","pages":"133-176"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13451166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146259416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
N Loubet, C Menéndez, A Verde, E Cuenca, S Accordino, L Alarcón, G Appignanesi
{"title":"Water: The Essential Liquid in Biophysics : From the Scrutiny of the Complex Nature of its Molecular Interactions to the Hydration Properties of Nanomaterials, Proteins and Membranes, and the Fingerprints of Hydrophobicity.","authors":"N Loubet, C Menéndez, A Verde, E Cuenca, S Accordino, L Alarcón, G Appignanesi","doi":"10.1007/978-3-032-24159-7_1","DOIUrl":"https://doi.org/10.1007/978-3-032-24159-7_1","url":null,"abstract":"<p><p>The simplicity of its molecular formula does not prevent water from exhibiting a complex behavior that becomes exacerbated under the hydration and nanoconfinement conditions typical of biological interfaces. In this chapter, we explore the molecular underpinnings of membrane hydration by examining a fundamental molecular principle: the interplay between local structure and energy that governs water's two-state interaction nature. We introduce the V<sub>4S</sub> index, a parameter-free, energy-based structural indicator capable of discriminating between tetrahedral coordination and hydrogen-bond (HB) defects-the two inherently preferred local environments in water. Crucially, we employ this metric to provide the first non-arbitrary molecular definition of hydrophobicity: \"hydrophobicity is the inability of a system to compensate for HB-defects in its hydration layer at the same energetic cost that bulk water pays for such defects (~ -6 kJ/mol, a value that amounts to only around 30% the energy of a typical HB)\". This absolute scale removes the subjective status of hydrophobicity, accurately signaling the θ = 90° contact angle transition and predicting drying regimes in nanoconfined spaces. Applying these concepts to biophysics, we show that the hydration shells of proteins and lipid membranes are significantly enriched in coordination defects compared to bulk water. These \"defect-type\" molecules are not stochastically distributed but concentrate at functional areas, such as protein binding sites. Finally, we present preliminary results on how this defect-enrichment characterizes the hydration of lipid membranes, offering a high-resolution tool (down to the single-atom level) to map local hydrophobicity and improve our understanding of molecular recognition and membrane permeability.</p>","PeriodicalId":21991,"journal":{"name":"Sub-cellular biochemistry","volume":"116 ","pages":"1-18"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148991308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Water at Lipid Interfaces: Domains and Defects.","authors":"María de Los Ángeles Frías, E Aníbal Disalvo","doi":"10.1007/978-3-032-24159-7_3","DOIUrl":"https://doi.org/10.1007/978-3-032-24159-7_3","url":null,"abstract":"<p><p>Water organized at the lipid membrane extends into the cell interior and reconciles the limited view of membrane function in the cellular context under the accepted current models. In this regard, the properties of the hydrated interphase play a fundamental role in the propagation of events between the membrane and the cytoplasm.Phosphate (-PO<sub>2</sub><sup>-</sup>) and carbonyl (-CO) phospholipid groups are specific hydration sites that modulate the arrangement of water molecules on the membrane surface. They form a network of H-bonds with specific thermodynamic, electrical, and mechanical properties. Its correlation gives rise place to cooperative and synergistic phenomena. Changes in water activity at the interphase can be produced by hydric, osmotic, saline stress, or metabolic events. Therefore, it is the thermodynamic link in a complex system that determines surface free energy and water-lipid interactions.The coordination of infrared spectroscopy coupled to attenuated total reflectance (FTIR/ATR) under controlled humidity and temperature conditions allowed to obtain information on the hydration state of lipid systems showing important details in the structure and properties that cannot be ignored to have a complete understanding of the thermodynamic behavior of lipid biomembranes.In this context, infrared spectroscopy permits to distinguish structural packing defects with special water arrangements where bioeffectors such as L-arginine (L-Arg) and L-phenylalanine (L-Phe) can be inserted.</p>","PeriodicalId":21991,"journal":{"name":"Sub-cellular biochemistry","volume":"116 ","pages":"43-73"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148991322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Collagen in Fibrotic Diseases.","authors":"Andrzej Fertala","doi":"10.1007/978-3-032-05273-5_11","DOIUrl":"10.1007/978-3-032-05273-5_11","url":null,"abstract":"<p><p>This chapter explores the role of fibrillar collagens, mainly collagen I, in developing fibrotic disorders associated with acute or chronic injuries. While collagen molecules' fundamental structure, composition, and intracellular biosynthesis steps remain similar in healthy and scar tissues, their extracellular architecture and physical properties significantly differ. These differences arise from the excessive production of collagen I and auxiliary proteins associated with collagen I folding and posttranslational modifications. As a result, the overaccumulation of collagen I-based fibrotic deposits creates a rigid mechanical environment that, through mechanotransduction, amplifies pro-fibrotic signaling in resident fibroblasts.In reviewing the literature, this chapter highlights key players that create, transmit, and sustain these signals, thereby perpetuating fibrosis. Given the growing recognition of mechanotransduction as a valid therapeutic target to limit fibrosis, this chapter also discusses strategies to inhibit different elements of this process. A significant challenge with these strategies is that both balanced and excessive scarring rely on the exact underlying mechanisms of scar tissue formation. Consequently, conventional anti-fibrotic agents may inadvertently impair the essential scarring needed to preserve tissue integrity after injury. Therefore, mechanotherapeutics that reduce collagen accumulation-driven scar stiffness represent a novel approach for developing more targeted anti-fibrotic therapies.</p>","PeriodicalId":21991,"journal":{"name":"Sub-cellular biochemistry","volume":"113 ","pages":"343-375"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146012332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Collagen Mechanics.","authors":"Phoebe Szarek, Jeffrey W Ruberti","doi":"10.1007/978-3-032-05273-5_10","DOIUrl":"10.1007/978-3-032-05273-5_10","url":null,"abstract":"<p><p>The collagen superfamily has evolved over nearly a billion years to produce a set of at least 28 proteins that are present in all vertebrates. Of these, the fibrillar collagens (Types I-III, V, XI, XIV, and XVII) comprise a diverse, fibrous structural polymer system that extensively invests and mechanically supports connective tissue. The chemistry, structure, and mechanics of single collagen molecules will be reviewed to provide insight into why collagen's triple helical motif is such an effective, efficient, and versatile structural building block. Review of the integration of molecular collagen into each successive length scale: fibrils, fibers, and tissues will show how the mechanical signature of each level in the hierarchy reflects the mechanical behavior of the smaller length scales from which it is composed. The remarkable structural and mechanical versatility of multiple whole connective tissues with completely different structural roles will demonstrate how each of them relies on collagen to perform their diverse mechanical functions. Finally, multiple themes that address more transcendent phenomena such as fibril diameter modulation, crosslinking, fatigue, and collagen mechanochemistry will be examined to provide a broader view of the field and open new directions for research.</p>","PeriodicalId":21991,"journal":{"name":"Sub-cellular biochemistry","volume":"113 ","pages":"277-342"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146012335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Dynamic Role of the Golgi Apparatus in Neuronal Function and Alzheimer's Disease.","authors":"Lou Fourriere, Paul A Gleeson","doi":"10.1007/978-3-032-16833-7_18","DOIUrl":"10.1007/978-3-032-16833-7_18","url":null,"abstract":"<p><p>The Golgi apparatus is a highly dynamic organelle and central to the regulation of a variety of cell processes. Here we review the relationship between the morphology and function of this organelle, especially to in relation to neuronal development and maintenance. The morphology of the Golgi organelle in neurons is unique as it is present as a Golgi ribbon in the cell body and also as dendritic Golgi elements, known as Golgi outposts, in the neuronal extensions. Many neurodegenerative diseases are associated with the loss of the Golgi ribbon structure and the appearance of dispersed and fragmented Golgi units in the cell body/soma. Here we summarise a key role of the Golgi to limit the proteolytic processing of amyloid precursor protein (APP) by secretases and protect healthy cells, and the perturbations of Golgi morphology arising from increased APP processing and amyloid β production in Alzheimer's disease, the most common of the neurodegenerative disease. The potential consequence of changes in the Golgi architecture and increase of amyloid β production on neuronal function is also considered.</p>","PeriodicalId":21991,"journal":{"name":"Sub-cellular biochemistry","volume":"111 ","pages":"441-462"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146259546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hanna Orlikowska-Rzeznik, Emilia Krok, Lukasz Piatkowski
{"title":"The Molecular Interplay Between Lipids, Cholesterol and Membrane Hydration Layer.","authors":"Hanna Orlikowska-Rzeznik, Emilia Krok, Lukasz Piatkowski","doi":"10.1007/978-3-032-24159-7_4","DOIUrl":"https://doi.org/10.1007/978-3-032-24159-7_4","url":null,"abstract":"<p><p>Understanding membrane structure, including its hydration, is vital for unraveling the chemistry of life. The nanoscopic layer of water directly hydrating biological membranes plays a critical role in maintaining cell structure, regulating biochemical processes, and mediating intermolecular interactions at the membrane interface. Cholesterol-rich lipid rafts, on the other hand, facilitate membrane fusion-a process essential for neurotransmitter release, fertilization, and viral entry-with localized, transient membrane dehydration serving as a key step in this process. This chapter summarizes the recent efforts to elucidate the intricate, three-way molecular interplay between membrane lipids, cholesterol, and the interfacial hydration layer. We begin by discussing the membrane-composition-specific effect of cholesterol on the arrangement of water molecules that form the membrane hydration layer. We highlight how interactions between cholesterol and different lipids lead to orientational anisotropy of the water molecules, resulting in a heterogeneous membrane dipole potential, which plays a role in domain-selective cellular processes, such as protein binding. Next, we consider the redistribution of cholesterol content within phase-separated lipid membranes induced by changes in the membrane's hydration state. This observation provides a new perspective on the regulatory role of cell membrane heterogeneity during membrane fusion. Finally, we discuss how to disentangle the ability of water and cholesterol to modulate lipid membranes' fluidity. The concluding remarks highlight pressing questions and key challenges that remain to be tackled in the field, paving the way for future research.</p>","PeriodicalId":21991,"journal":{"name":"Sub-cellular biochemistry","volume":"116 ","pages":"75-97"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148991324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}