Biochemical Society transactions最新文献_第3页

Disruption of BDNF signalling in neuropathologies. 神经病理中BDNF信号的中断。

IF 4.3 3区生物学

Biochemical Society transactions Pub Date : 2026-02-25 DOI: 10.1042/BST20253079

Aurélie Paulo-Ramos, Elena R Rhymes, David Villarroel-Campos, James N Sleigh

引用次数: 0

Microtubule inner proteins in apicomplexan parasites. 顶复合体寄生物的微管内蛋白。

IF 4.3 3区生物学

Biochemical Society transactions Pub Date : 2026-02-02 DOI: 10.1042/BST20253110

Annika M Binder, Friedrich Frischknecht, Franziska Hentzschel

{"title":"Microtubule inner proteins in apicomplexan parasites.","authors":"Annika M Binder, Friedrich Frischknecht, Franziska Hentzschel","doi":"10.1042/BST20253110","DOIUrl":"10.1042/BST20253110","url":null,"abstract":"Microtubule inner proteins (MIPs) are integral components within the microtubule lumen of various organisms, contributing to microtubule structural integrity and functionality. Apicomplexan parasites, including Plasmodium spp. and Toxoplasma gondii, exhibit a range of specialized tubulin structures, such as axonemal microtubules, subpellicular microtubules (SPMTs), and conoid fibers, playing critical roles in cellular morphology and motility. Yet, in contrast with model organisms, only a few MIPs have been characterized in apicomplexans so far. Recent advances in cryo-electron tomography and structural proteomics have facilitated the study of MIPs, shedding light on unique adaptations that distinguish apicomplexan microtubules from those in model eukaryotes. Key findings include the identification of an interrupted luminal helix in SPMTs, which is critical for stabilizing microtubules under stress. The relatively small repertoire of axonemal MIPs contrasts markedly with the numerous MIPs observed in other systems, possibly reflecting adaptations for rapid microtubule assembly without intraflagellar transport. Furthermore, emerging evidence points to multiple MIPs within the conoid and SPMTs, suggesting further roles for MIPs in these parasites. This review highlights the currently known contributions of MIPs to the survival and proliferation of these parasites, while emphasizing the need for continued research to fully characterize their diverse roles and molecular mechanisms.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"54 2","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12905489/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146103692","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}

引用次数: 0

Plasticity and stringency: rethinking stem cell division modes. 可塑性与严密性：对干细胞分裂模式的反思。

IF 4.3 3区生物学

Biochemical Society transactions Pub Date : 2026-02-02 DOI: 10.1042/BST20250202

Muhammed Burak Bener, Mayu Inaba

引用次数: 0

Mechanisms of transcriptional regulation of CCR5, which is the co-receptor for R5-tropic HIV and is also involved in other disease processes. CCR5的转录调控机制，CCR5是嗜r5型HIV的共受体，也参与其他疾病过程。

IF 4.3 3区生物学

Biochemical Society transactions Pub Date : 2026-01-28 DOI: 10.1042/BST20253092

Lingyun Wang, Sharon Veron Akisa, Richard Sutton

{"title":"Mechanisms of transcriptional regulation of CCR5, which is the co-receptor for R5-tropic HIV and is also involved in other disease processes.","authors":"Lingyun Wang, Sharon Veron Akisa, Richard Sutton","doi":"10.1042/BST20253092","DOIUrl":"10.1042/BST20253092","url":null,"abstract":"C-C chemokine receptor type 5 (CCR5) is the R5-tropic human immunodeficiency virus type 1 or HIV co-receptor. Lower CCR5 levels can reduce T cell and macrophage susceptibility and suppress HIV infection. Moreover, CCR5Δ32 homozygous stem cell transplantation is central to HIV cure. Other studies have shown that CCR5 plays a vital role in cancer development and cell migration, and it was considered a potential therapeutic target for several types of malignancy. In addition to HIV and cancer, CCR5 also participates in immune response and plays a role in graft-versus-host disease in bone marrow transplant patients. It is also associated with other diseases, such as Parkinson's disease and rheumatoid arthritis. Thus, investigating its regulatory mechanisms is critically important for understanding the progress and therapeutics of other illnesses. Transcriptional regulation of genes is a complex process that controls when, where, and how much the RNA transcript is produced. In this minireview, we discuss epigenetic regulatory mechanisms, such as DNA methylation and histone modification, transcription factors, and signal transduction pathways, involved in the regulation of CCR5 transcripts.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"54 1","pages":"95-106"},"PeriodicalIF":4.3,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12905492/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146199827","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}

引用次数: 0

Advances in understanding Ton and Tol system motor proteins. Ton和Tol系统运动蛋白的研究进展。

IF 4.3 3区生物学

Biochemical Society transactions Pub Date : 2026-01-28 DOI: 10.1042/BST20253128

Herve Celia, Susan K Buchanan, Istvan Botos

引用次数: 0

A phase separation hypothesis for the biological function of PrP: the role of multivalent interactions at the plasma membrane. PrP生物学功能的相分离假说：质膜上多价相互作用的作用。

IF 4.3 3区生物学

Biochemical Society transactions Pub Date : 2026-01-28 DOI: 10.1042/BST20253081

Maria Heloisa Freire, Rafael Linden, Yraima Cordeiro

{"title":"A phase separation hypothesis for the biological function of PrP: the role of multivalent interactions at the plasma membrane.","authors":"Maria Heloisa Freire, Rafael Linden, Yraima Cordeiro","doi":"10.1042/BST20253081","DOIUrl":"10.1042/BST20253081","url":null,"abstract":"Although the prion protein (PrP) is well established as the etiological agent of transmissible spongiform encephalopathies, its biological function remains under debate. Native, cellular PrP (PrPC) is a glycosylphosphatidylinositol-anchored protein that interacts with various proteins and other molecular ligands at the cell surface, triggering diverse cellular responses such as neuritogenesis and neuroprotection. PrPC has been proposed to act as a scaffolding protein, facilitating the assembly of multicomponent complexes at the membrane, with signal transduction occurring through the recruitment of transmembrane proteins. Recent findings demonstrate that PrP undergoes phase separation (PS) in vitro and in cellulo, mostly driven by its multivalency, intrinsically disordered N-terminal domain, and ability to bind polyanions. Considering recent data showing that membrane multicomponent complexes may assemble through PS, we discuss the possible formation of biomolecular condensates containing PrP at the membrane in light of previously described PrP protein ligands. In this mini-review, we examine PrP's interactions with key ligands such as epidermal growth factor receptor, apolipoprotein E, amyloid β oligomers, α-synuclein, N-methyl-D-aspartate receptor, postsynaptic density protein 95, integrin β1, and tau, assessing their relevance in PS-mediated condensate formation. These proteins were selected based on their direct or indirect interaction with PrP, biological effects, presence in a membrane environment, and evidence of participation in biomolecular condensates. Based on current evidence, we propose that PS may be a fundamental mechanism underlying PrP's biological role in the membrane.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"54 1","pages":"83-93"},"PeriodicalIF":4.3,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12905493/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146199569","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}

引用次数: 0

Lipids regulate epidermal growth factor receptor activation by its ligands. 脂质通过其配体调节表皮生长因子受体的激活。

IF 4.3 3区生物学

Biochemical Society transactions Pub Date : 2026-01-22 DOI: 10.1042/BST20253090

James M Hutchison, Mark A Lemmon

{"title":"Lipids regulate epidermal growth factor receptor activation by its ligands.","authors":"James M Hutchison, Mark A Lemmon","doi":"10.1042/BST20253090","DOIUrl":"10.1042/BST20253090","url":null,"abstract":"The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that has garnered extensive interest since its discovery as an oncogene product in the 1980s. We now understand that the binding of soluble growth factors to EGFR activates it by facilitating receptor-mediated EGFR dimerization. However, how the extracellular ligand-binding and intracellular tyrosine kinase domains communicate across the bilayer remains unclear. This lack of understanding likely originates from a 'divide and conquer' approach that has provided a detailed understanding of the respective domains in isolation but only limited knowledge of how they are co-ordinated during signaling. Attempts to study full-length EGFR in detergents or membrane environments that lack possible key lipid cofactors leave a critical component of intact receptor signaling understudied. Indeed, multiple classes of lipids, such as gangliosides and PtdIns(4,5)P2, have long been known to influence EGFR signaling in cells, and a lack of their inclusion in in vitro studies has hindered mechanistic understanding of the intact receptor. This review highlights recent studies of how lipids regulate EGFR activity, with special attention paid to potentially actionable co-dependent lipid metabolism in glioblastoma multiforme and promising new methods for studying membrane protein-bilayer interactions.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"54 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12905494/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146017237","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}

引用次数: 0

Loop dynamics, allostery, and function in protein tyrosine phosphatases: insights from molecular simulations. 蛋白酪氨酸磷酸酶的循环动力学、变构和功能：来自分子模拟的见解。

IF 4.3 3区生物学

Biochemical Society transactions Pub Date : 2026-01-21 DOI: 10.1042/BST20250018

Colin L Welsh, Shina Caroline Lynn Kamerlin

{"title":"Loop dynamics, allostery, and function in protein tyrosine phosphatases: insights from molecular simulations.","authors":"Colin L Welsh, Shina Caroline Lynn Kamerlin","doi":"10.1042/BST20250018","DOIUrl":"10.1042/BST20250018","url":null,"abstract":"Enzymes are dynamic entities, and their conformational dynamics are intimately linked to their function and evolvability. In this context, protein tyrosine phosphatases (PTPs) are an excellent model system to probe the role of conformational dynamics in enzyme function and evolution. They are a genetically diverse family of enzymes, with a highly conserved catalytic domain, identical catalytic mechanisms, and turnover numbers that vary by orders of magnitude, with their activity being determined by the mobility of a catalytic loop that closes over the active site and places a key catalytic residue in place for efficient catalysis. From a biological perspective, PTPs are important regulators of a host of cellular processes, including cellular signaling, which has made them in particular important anticancer drug targets, among other diseases of interest. The high structural conservation of their active sites renders them therapeutically elusive, but there exist allosteric inhibitors that exploit the allosteric regulation of these enzymes to impede the motion of their catalytic WPD-loops, thus inactivating them. Conformational dynamics and allostery are problems that are ideal for computational investigation, and indeed, advances in computational methodologies have resulted in a range of exciting studies illuminating the molecular details of structure-function-dynamics-allostery links in these enzymes. This review provides both a brief history of computational work in this space, as well as discussing in detail recent advances, illustrating how molecular simulations have been successfully exploited to enhance our fundamental understanding of these biomedically important enzymes, and of the function and regulation of 'loopy' enzymes more broadly.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"54 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12905499/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146008735","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}

引用次数: 0

Regulation of renal aquaporins: implications in tubular epithelial integrity. 肾水通道蛋白的调控：对小管上皮完整性的影响。

IF 4.3 3区生物学

Biochemical Society transactions Pub Date : 2026-01-12 DOI: 10.1042/BST20253114

Vishalini Venkatesan, Charlotte M Sørensen, Emma Tina B Olesen

{"title":"Regulation of renal aquaporins: implications in tubular epithelial integrity.","authors":"Vishalini Venkatesan, Charlotte M Sørensen, Emma Tina B Olesen","doi":"10.1042/BST20253114","DOIUrl":"10.1042/BST20253114","url":null,"abstract":"Aquaporins (AQPs) are crucial membrane proteins that primarily facilitate water transport across cell membranes. In the kidneys, AQP1, AQP7, AQP8, and AQP11 are expressed in the proximal tubules. AQP1 is also localized to the thin descending limb of the loop of Henle. AQP2, AQP3, AQP4, AQP5, and AQP6 are expressed in the collecting ducts. Specific AQPs, such as aquaglyceroporins and peroxiporins, also transport solutes like glycerol and hydrogen peroxide, indicating their broader physiological roles beyond water permeability. Renal AQPs play a fundamental role in urine concentration and maintaining water balance. However, some studies using AQP knockout mouse models have reported structural abnormalities in the renal tubules, along with defective water handling. These findings highlight the involvement of AQPs in regulating cell proliferation, migration, and apoptosis, which are essential processes for maintaining tubular integrity. Furthermore, aquaglyceroporins and peroxiporins are implicated in modulating cellular redox balance and contributing to oxidative stress responses that are also associated with tubular damage. This review explores how AQPs are regulated under physiological conditions and how they become dysregulated in kidney diseases such as acute kidney injury, diabetic kidney disease, and polycystic kidney disease. Understanding these mechanisms may help in identifying new therapeutic strategies targeting AQPs in renal pathologies.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"54 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12862957/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145958525","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}

引用次数: 0

Targeting opportunities presented by the pyrimidine biosynthesis pathway in Mycobacterium tuberculosis: a brief review. 嘧啶生物合成途径在结核分枝杆菌中的靶向机会：简要综述。

IF 4.3 3区生物学

Biochemical Society transactions Pub Date : 2026-01-12 DOI: 10.1042/BST20253113

Marta Alberti, Riccardo Miggiano

{"title":"Targeting opportunities presented by the pyrimidine biosynthesis pathway in Mycobacterium tuberculosis: a brief review.","authors":"Marta Alberti, Riccardo Miggiano","doi":"10.1042/BST20253113","DOIUrl":"10.1042/BST20253113","url":null,"abstract":"Mycobacterium tuberculosis (MTB) is the etiologic agent of tuberculosis (TB) in humans, an infectious disease that continues to be a significant global health concern. The long-term use of multiple anti-tubercular agents may result in patient non-compliance and increased drug toxicity, which could contribute to the emergence of drug-resistant MTB strains that are not susceptible even to second-line available drugs. It is therefore imperative that new antitubercular drugs and vaccines are developed. The peculiar traits of MTB, such as the biochemical and structural features of vital metabolic pathways, can be assessed to identify possible targets for drug development. Enzymes involved in pyrimidine metabolism may be suitable drug targets for TB, given that this pathway is essential for mycobacteria and comprises enzymes that differ from those found in humans. Here, we focused on reviewing the state of the art concerning the therapeutic opportunities presented by the pyrimidine biosynthetic pathway (PBP) as a potential source of enzymes that could be targeted for the treatment of TB. We selected essential enzymes belonging to the PBP for which we identified the existence of a drug discovery pipeline at both the preclinical and clinical levels. Moreover, we emphasize the biochemical and structural characteristics that are pertinent to the development of pharmaceutical agents. These include the molecular details that can ensure selectivity towards the pathogen's proteins.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":"54 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12862964/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145958537","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}

引用次数: 0