{"title":"Structural glycobiology - from enzymes to organelles.","authors":"Courtney J Mycroft-West, Miron A Leanca, Liang Wu","doi":"10.1042/BST20241119","DOIUrl":"https://doi.org/10.1042/BST20241119","url":null,"abstract":"<p><p>Biological carbohydrate polymers represent some of the most complex molecules in life, enabling their participation in a huge range of physiological functions. The complexity of biological carbohydrates arises from an extensive enzymatic repertoire involved in their construction, deconstruction and modification. Over the past decades, structural studies of carbohydrate processing enzymes have driven major insights into their mechanisms, supporting associated applications across medicine and biotechnology. Despite these successes, our understanding of how multienzyme networks function to create complex polysaccharides is still limited. Emerging techniques such as super-resolution microscopy and cryo-electron tomography are now enabling the investigation of native biological systems at near molecular resolutions. Here, we review insights from classical in vitro studies of carbohydrate processing, alongside recent in situ studies of glycosylation-related processes. While considerable technical challenges remain, the integration of molecular mechanisms with true biological context promises to transform our understanding of carbohydrate regulation, shining light upon the processes driving functional complexity in these essential biomolecules.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"53 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070886","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":"Beyond the mono-nucleosome.","authors":"Juliana Kikumoto Dias, Sheena D'Arcy","doi":"10.1042/BST20230721","DOIUrl":"https://doi.org/10.1042/BST20230721","url":null,"abstract":"<p><p>Nucleosomes, the building block of chromatin, are responsible for regulating access to the DNA sequence. This control is critical for essential cellular processes, including transcription and DNA replication and repair. Studying chromatin can be challenging both in vitro and in vivo, leading many to use a mono-nucleosome system to answer fundamental questions relating to chromatin regulators and binding partners. However, the mono-nucleosome fails to capture essential features of the chromatin structure, such as higher-order chromatin folding, local nucleosome-nucleosome interactions, and linker DNA trajectory and flexibility. We briefly review significant discoveries enabled by the mono-nucleosome and emphasize the need to go beyond this model system in vitro. Di-, tri-, and tetra-nucleosome arrays can answer important questions about chromatin folding, function, and dynamics. These multi-nucleosome arrays have highlighted the effects of varying linker DNA lengths, binding partners, and histone post-translational modifications in a more chromatin-like environment. We identify various chromatin regulatory mechanisms yet to be explored with multi-nucleosome arrays. Combined with in-solution biophysical techniques, studies of minimal multi-nucleosome chromatin models are feasible.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"53 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063316","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}
Rebeca Martínez-Lazaro, Andrea Reyes-Carrión, David Bartolomé-Martín, Teresa Giraldez
{"title":"The NMDAR-BK channelosomes as regulators of synaptic plasticity.","authors":"Rebeca Martínez-Lazaro, Andrea Reyes-Carrión, David Bartolomé-Martín, Teresa Giraldez","doi":"10.1042/BST20240425","DOIUrl":"10.1042/BST20240425","url":null,"abstract":"<p><p>Large conductance voltage- and calcium-activated potassium channels (BK channels) are extensively found throughout the central nervous system and play a crucial role in various neuronal functions. These channels are activated by a combination of cell membrane depolarisation and an increase in intracellular calcium concentration, provided by calcium sources located close to BK. In 2001, Isaacson and Murphy first demonstrated the coupling of BK channels with N-methyl-D-aspartate receptors (NMDAR) in olfactory bulb neurons. Since then, additional evidence has confirmed this functional coupling in other brain regions and highlighted its significance in neuronal function and pathophysiology. In this review, we explore the current understanding of these macrocomplexes in the brain, the molecular mechanisms behind their interactions and their potential roles in neurodevelopmental disorders, paving the way for new treatment strategies.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"53 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051454","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}
Rajendra K Angara, Peyton E Van Winkle, Stacey D Gilk
{"title":"Mechanisms of lipid homeostasis in the Coxiella Containing Vacuole.","authors":"Rajendra K Angara, Peyton E Van Winkle, Stacey D Gilk","doi":"10.1042/BST20240899","DOIUrl":"https://doi.org/10.1042/BST20240899","url":null,"abstract":"<p><p>Coxiella burnetii, the causative agent of human Q fever, is an obligate intracellular bacterial pathogen that replicates in a large, membrane-bound vacuole known as the Coxiella Containing Vacuole (CCV). The CCV is a unique, phagolysosome-derived vacuole with a sterol-rich membrane containing host and bacterial proteins. The CCV membrane itself serves as a barrier to protect the bacteria from the host's innate immune response, and the lipid and protein content directly influence both the CCV luminal environment and interactions between the CCV and host trafficking pathways. CCV membrane cholesterol is critical in regulating CCV pH, while CCV phosphatidylinositol phosphate species influence CCV fusion events and membrane dynamics. C. burnetii proteins directly target host lipid metabolism to regulate CCV membrane content and generate a source of lipids that support bacterial replication or influence the innate immune response. This review provides an overview of the diverse repertoire of lipids involved in CCV formation and maintenance, highlighting the pathogen-driven strategies to modify host lipid homeostasis.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"0 0","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143031913","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":"Greasing the wheels of inflammasome formation: regulation of NLRP3 function by S-linked fatty acids.","authors":"Daniel M Williams, Andrew A Peden","doi":"10.1042/BST20241738","DOIUrl":"https://doi.org/10.1042/BST20241738","url":null,"abstract":"<p><p>NLRP3 is an inflammasome seeding pattern recognition receptor that initiates a pro-inflammatory signalling cascade in response to changes in intracellular homeostasis that are indicative of bacterial infection or tissue damage. Several types of post-translational modification (PTM) have been identified that are added to NLRP3 to regulate its activity. Recent progress has revealed that NLRP3 is subject to a further type of PTM, S-acylation (or palmitoylation), which involves the reversible addition of long-chain fatty acids to target cysteine residues by opposing sets of enzymes. This review provides an overview of recent studies that have identified S-acylation as an important modifier of NLRP3 function. The essential role of S-acylation in the recruitment of NLRP3 to intracellular membranes and the consequences of S-acylation-dependent membrane recruitment on NLRP3 localisation and activation are discussed in detail.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142999338","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":"Constructing mechanosensitive signalling pathways de novo in synthetic cells.","authors":"James W Hindley","doi":"10.1042/BST20231285","DOIUrl":"https://doi.org/10.1042/BST20231285","url":null,"abstract":"<p><p>Biological mechanotransduction enables cells to sense and respond to mechanical forces in their local environment through changes in cell structure and gene expression, resulting in downstream changes in cell function. However, the complexity of living systems obfuscates the mechanisms of mechanotransduction, and hence the study of these processes in vitro has been critical in characterising the function of existing mechanosensitive membrane proteins. Synthetic cells are biomolecular compartments that aim to mimic the organisation, functionality and behaviours of biological systems, and represent the next step in the development of in vitro cell models. In recent years, mechanosensitive channels have been incorporated into synthetic cells to create de novo mechanosensitive signalling pathways. Here, I will discuss these developments, from the molecular parts used to construct existing pathways, the functionality of such systems, and potential future directions in engineering synthetic mechanotransduction. The recapitulation of mechanotransduction in synthetic biology will facilitate an improved understanding of biological signalling through the study of molecular interactions across length scales, whilst simultaneously generating new biotechnologies that can be applied as diagnostics, microreactors and therapeutics.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142999320","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":"How parental factors shape the plant embryo.","authors":"Alexa-Maria Wangler, Martin Bayer","doi":"10.1042/BST20240369","DOIUrl":"https://doi.org/10.1042/BST20240369","url":null,"abstract":"<p><p>Primary axis formation is the first step of embryonic patterning in flowering plants and recent findings highlight the importance of parent-of-origin effects in this process. Apical-basal patterning has a strong influence on suspensor development, an extra-embryonic organ involved in nutrient transport to the embryo at an early stage of seed development. The endosperm, a second fertilization product, nourishes the embryo at later stages of seed development. Parent-of-origin effects are phenotypic effects that depend on whether a causal gene is inherited from the mother or the father. They are discussed in the context of the parental conflict theory in relation to nutrient allocation to the offspring. Imprinting is an important mechanism leading to uniparental gene expression in the endosperm and maternal control of its development. The parental conflict theory would predict that, with limited resources available, there is a competition between paternal alleles to increase nutrient supply, allowing rapid development and seed filling. A parental conflict might therefore shape the evolution of genes that can influence the allocation of nutrients to the seeds. However, we will also discuss other possible causes that might select genes for uniparental contribution. New data show that parent-of-origin effects also occur during the early stages of embryo development. These appear to be caused primarily by the carry-over of gamete-derived factors. In this review, we will highlight the molecular pathways that control apical-basal patterning in the early embryo and discuss recent findings in the context of the parental conflict theory and alternative explanations.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142999433","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":"A framework for understanding and investigating polyphosphate-protein interactions.","authors":"Liam McCarthy, Kanchi Baijal, Michael Downey","doi":"10.1042/BST20240678","DOIUrl":"https://doi.org/10.1042/BST20240678","url":null,"abstract":"<p><p>Many prokaryotic and eukaryotic cells store inorganic phosphate in the form of polymers called polyphosphate (polyP). There has been an explosion of interest in polyP over the past decade, in part due to newly suggested roles related to diverse aspects of human health. The physical interaction of polyP chains with specific proteins has been proposed to regulate cellular homeostasis and modulate signaling pathways in response to environmental changes. Recently, several studies have challenged existing models for how polyP interacts with its protein targets, while identifying new motifs that are capable of binding to polyP. In this review, we summarize these findings, delineate the functional implications for polyP-protein interactions at the molecular level, and define open questions that should be addressed to propel the field forward.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142999318","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}
Natalie Koh, Zhengyu Ma, Abhishek Sarup, Amy C Kristl, Mark Agrios, Margaret Young, Andrew Miri
{"title":"Selective direct motor cortical influence during naturalistic climbing in mice.","authors":"Natalie Koh, Zhengyu Ma, Abhishek Sarup, Amy C Kristl, Mark Agrios, Margaret Young, Andrew Miri","doi":"10.1101/2023.06.18.545509","DOIUrl":"10.1101/2023.06.18.545509","url":null,"abstract":"<p><p>It remains poorly resolved when and how motor cortical output directly influences limb muscle activity through descending projections, which impedes mechanistic understanding of cortical movement control. Here we addressed this in mice performing an ethologically inspired all-limb climbing behavior. We quantified the direct influence of forelimb primary motor cortex (caudal forelimb area, CFA) on muscle activity across the muscle activity states that occur during climbing. We found that CFA instructs muscle activity pattern, mainly by selectively activating certain muscles while exerting much smaller, bidirectional effects on their antagonists. From Neuropixel recordings, we identified linear combinations (components) of motor cortical activity that covary with these effects, finding that these components differ partially from those that covary with muscle activity and differ almost completely from those that covary with kinematics. Collectively, our results reveal an instructive direct motor cortical influence on limb muscles that is selective within a motor behavior and reliant on a distinct neural activity subspace.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"17 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11370436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80178576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Oda Helene Schiøtz, Sven Klumpe, Juergen M Plitzko, Christoph J O Kaiser
{"title":"Cryo-electron tomography: en route to the molecular anatomy of organisms and tissues.","authors":"Oda Helene Schiøtz, Sven Klumpe, Juergen M Plitzko, Christoph J O Kaiser","doi":"10.1042/BST20240173","DOIUrl":"10.1042/BST20240173","url":null,"abstract":"<p><p>Cryo-electron tomography (cryo-ET) has become a key technique for obtaining structures of macromolecular complexes in their native environment, assessing their local organization and describing the molecular sociology of the cell. While microorganisms and adherent mammalian cells are common targets for tomography studies, appropriate sample preparation and data acquisition strategies for larger cellular assemblies such as tissues, organoids or small model organisms have only recently become sufficiently practical to allow for in-depth structural characterization of such samples in situ. These advances include tailored lift-out approaches using focused ion beam (FIB) milling, and improved data acquisition schemes. Consequently, cryo-ET of FIB lamellae from large volume samples can complement ultrastructural analysis with another level of information: molecular anatomy. This review highlights the recent developments towards molecular anatomy studies using cryo-ET, and briefly outlines what can be expected in the near future.</p>","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"2415-2425"},"PeriodicalIF":3.8,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11668301/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142783957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}