Biological Chemistry最新文献_第3页

Actin scaffolds as organizers of presynaptic function, assembly and plasticity across species. 肌动蛋白支架作为跨物种突触前功能、组装和可塑性的组织者。

IF 2.5 4区生物学

Biological Chemistry Pub Date : 2026-07-08 Print Date: 2026-07-24 DOI: 10.1515/hsz-2026-0120

Stephan J Sigrist, Astrid G Petzoldt

{"title":"Actin scaffolds as organizers of presynaptic function, assembly and plasticity across species.","authors":"Stephan J Sigrist, Astrid G Petzoldt","doi":"10.1515/hsz-2026-0120","DOIUrl":"10.1515/hsz-2026-0120","url":null,"abstract":"The presynapse is a highly specialized neuronal compartment whose organizational core, the active zone, coordinates the precisely regulated neurotransmitter release. The function, assembly, maturation and remodeling of presynapses are fundamental to brain function, underlying circuit development, synaptic plasticity and memory formation. Central to these processes is a dynamic actin cytoskeletal scaffold that integrates structural organization with synaptic vesicle exo- and endocytosis, thereby coupling molecular architecture to synaptic release. We summarize decades of work across vertebrate and invertebrate model systems to delineate how local, activity-dependent reorganization of the actin cytoskeletal modulates presynaptic function, assembly, and plasticity. We depict the molecular mechanism by which actin networks coordinate, in a developmental stage-dependent manner, nearly every part of the synaptic vesicle cycle and include a focus on myosin family proteins, as actin-based motor protein. Furthermore, we review the bidirectional interplay between presynaptic active zone proteins and the local presynaptic actin network. Finally, we focus on the role of actin scaffolds in synaptogenesis and how local actin regulation is coupled to nanoscale active zone organization and large-scale presynaptic terminal structure at the uniquely accessible and mechanistically informative Drosophila neuromuscular junction.","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":"125-150"},"PeriodicalIF":2.5,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148403423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Neuronal membrane organization by the submembranous spectrin-ankyrin scaffold: evolution, specialization and disease. 膜下谱蛋白-锚蛋白支架的神经元膜组织：进化、特化和疾病。

IF 2.5 4区生物学

Biological Chemistry Pub Date : 2026-06-03 Print Date: 2026-07-24 DOI: 10.1515/hsz-2026-0117

Maximilian Goy, Jan Pielage

{"title":"Neuronal membrane organization by the submembranous spectrin-ankyrin scaffold: evolution, specialization and disease.","authors":"Maximilian Goy, Jan Pielage","doi":"10.1515/hsz-2026-0117","DOIUrl":"10.1515/hsz-2026-0117","url":null,"abstract":"Neuronal function relies on precise compartmentalization into dendritic, somatic, axonal, and synaptic domains that require specialized cellular architectures. Axons, in particular, can extend over extraordinary distances while preserving stable membrane composition, mechanical integrity, and reliable excitability. A submembranous scaffold composed of spectrin, ankyrin, actin, and associated proteins provides a conserved platform for coupling membrane proteins to cytoskeletal support and organizing membrane domains. In axons, this scaffold assembles into a membrane-associated periodic skeleton (MPS) with near-regular spacing that supports mechanical load, patterns membrane components, and contributes to compartmental boundaries. Comparative genetics indicates that core principles of spectrin-ankyrin organization are ancient, whereas vertebrate evolution expanded spectrin and ankyrin families and enabled specialized excitable domains such as the axon initial segment (AIS) and nodes of Ranvier. Pathogenic variants in spectrin and ankyrin genes disrupt neuronal development and excitability and cause a growing spectrum of neurodevelopmental and neurodegenerative disorders, underscoring scaffold integrity as a key determinant of circuit stability. Here, we examine how conserved spectrin-ankyrin scaffold principles were adapted to neuronal cell-type diversity and domain specialization, with emphasis on axons, synapses, and disease, and we discuss how the membrane-associated periodic skeleton may function not only as a stabilizing framework but also as a nanoscale organizer of neuronal membrane architecture.","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":"217-233"},"PeriodicalIF":2.5,"publicationDate":"2026-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148147926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Golgi-associated membrane scaffolds: roles in health and disease. 高尔基蛋白相关膜支架：在健康和疾病中的作用

IF 2.5 4区生物学

Biological Chemistry Pub Date : 2026-05-26 Print Date: 2026-07-24 DOI: 10.1515/hsz-2025-0242

Thilo Speckmann, Judith Saurenbach, Annette Schürmann

引用次数: 0

Cysteine cathepsin proteases in apicomplexan parasites. 顶复合体寄生虫的半胱氨酸组织蛋白酶蛋白酶。

IF 2.4 4区生物学

Biological Chemistry Pub Date : 2026-05-07 DOI: 10.1515/hsz-2025-0240

Antoine Mayté, Anne Silvestre, Florian Veillard, Sonia Lacroix-Lamandé, Gilles Lalmanach, Julie Tottey

{"title":"Cysteine cathepsin proteases in apicomplexan parasites.","authors":"Antoine Mayté, Anne Silvestre, Florian Veillard, Sonia Lacroix-Lamandé, Gilles Lalmanach, Julie Tottey","doi":"10.1515/hsz-2025-0240","DOIUrl":"https://doi.org/10.1515/hsz-2025-0240","url":null,"abstract":"Cysteine cathepsins are papain-like proteases which play key roles in a large range of organisms, including apicomplexan parasites. These obligate endoparasites are responsible for many devastating diseases in human and/or animal hosts, for which available treatments are limited or face the emergence of resistance. This review presents the cysteine cathepsins expressed by five major Apicomplexa (Plasmodium falciparum, Cryptosporidium parvum, Toxoplasma gondii, Eimeria tenella and Babesia bovis), highlighting available data on their structures, specific or common features, and biological functions in the parasite biology and host-parasite interactions. Although they belong to the same phylum, apicomplexan parasites have very distinct life cycles and biology, which are well adapted to the hosts they infect and to the tissues within which they develop. Accordingly, apicomplexan cysteine cathepsins display a wide variety of functions, associated with shared (e.g., invasion of and egress from host cells) or unique (e.g., degradation of haemoglobin in P. falciparum) biological pathways. Through their crucial functions and involvement in multiple parasite stages, these parasitic proteases represent assumed therapeutic targets. The description of apicomplexan cysteine cathepsins also appears uneven within the phylum, and further exploration of their biology and role is needed to drive novel preventive or curative intervention strategies.","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147855624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mechanistic insights on spatiotemporal control of Ras-signaling. ras -信号时空控制机制研究。

IF 2.5 4区生物学

Biological Chemistry Pub Date : 2026-05-04 Print Date: 2026-05-26 DOI: 10.1515/hsz-2025-0243

Clotilde Charrier, Sascha Mrachacz, Sabrina Schulze, Michael Lammers

{"title":"Mechanistic insights on spatiotemporal control of Ras-signaling.","authors":"Clotilde Charrier, Sascha Mrachacz, Sabrina Schulze, Michael Lammers","doi":"10.1515/hsz-2025-0243","DOIUrl":"10.1515/hsz-2025-0243","url":null,"abstract":"Proteins of the Ras-family are guanine nucleotide binding proteins (GNBPs) involved in a variety of fundamental cellular processes, including cell proliferation, cell differentiation, cytoskeleton dynamics, vesicular processes and intracellular transport. A dysregulation of Ras-signaling has been found to be causative for the development of diseases, such as diverse cancer types, RASopathies, neurodegenerative diseases and ciliopathies. Ras-proteins cycle between a GTP-bound on-state and a GDP-bound off-state. Ras-proteins show low intrinsic rates for nucleotide exchange and nucleotide hydrolysis. They need guanine-nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs) to accelerate both functions in order to act as true molecular switches in the physiological context. Ras-proteins and their regulators/effectors are targets of post-translational modifications (PTMs) such as phosphorylation, ac(et)ylation, lipidation and ubiquitination. These PTMs regulate their activity, subcellular localization and turnover. In a biological perspective, PTMs are essential components for cellular signaling cascades and for molecular pattern formation. Bacterial pathogens use PTMs of Ras-proteins to allow efficient infection processes. Besides, modifications of Ras-proteins were shown to be of therapeutic potential in oncogenic variants such as Ras G12C. In this review, we summarize current knowledge on Ras-signaling, while emphasizing PTMs as dynamic signaling hubs for its precise spatiotemporal control.","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":"407 1-3","pages":"25-66"},"PeriodicalIF":2.5,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147863242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Electron donating and withdrawing groups affect the antioxidant activity of 4'-aminochalcones on gentamicin-induced kidney cell injury. 给、取电子基团影响4′-氨基查尔酮对庆大霉素所致肾细胞损伤的抗氧化活性。

IF 2.4 4区生物学

Biological Chemistry Pub Date : 2026-04-23 DOI: 10.1515/hsz-2025-0218

Igor Moreira de Almeida, Akenaton Onassis Cardoso Viana Gomes, Arif Ali, Emanuel Paula Magalhães, Emmanuel Silva Marinho, Felipe Ramos Alexandre, Hélcio Silva Dos Santos, Márcia Machado Marinho, Ramon Róseo Paula Pessoa Bezerra de Menezes, Stephanie Alves Veloso, Tiago Lima Sampaio, Alice Maria Costa Martins

{"title":"Electron donating and withdrawing groups affect the antioxidant activity of 4'-aminochalcones on gentamicin-induced kidney cell injury.","authors":"Igor Moreira de Almeida, Akenaton Onassis Cardoso Viana Gomes, Arif Ali, Emanuel Paula Magalhães, Emmanuel Silva Marinho, Felipe Ramos Alexandre, Hélcio Silva Dos Santos, Márcia Machado Marinho, Ramon Róseo Paula Pessoa Bezerra de Menezes, Stephanie Alves Veloso, Tiago Lima Sampaio, Alice Maria Costa Martins","doi":"10.1515/hsz-2025-0218","DOIUrl":"https://doi.org/10.1515/hsz-2025-0218","url":null,"abstract":"Gentamicin (GM)-induced nephrotoxicity is closely linked to oxidative stress, with few therapeutic alternatives available. Chalcones are structurally versatile compounds with reported antioxidant properties, making them attractive candidates for nephroprotection. The 4'-aminochalcones substituted with p-NO2 (31.25-15.62 µM) or p-N(CH3)2 (7.81 µM) groups demonstrated significant protective effects, partially restoring (∼11 %) HK-2 cell viability after GM-induced injury. Both derivatives increased intracellular glutathione levels, reduced superoxide accumulation, and lowered cytoplasmic ROS concentration. Structural and electronic analyses revealed that the electron-donating group p-N(CH3)2 enhanced antioxidant reactivity, whereas the electron-withdrawing group p-NO2 decreased cytotoxicity. HK-2 cells were exposed to GM (IC50 = 5.0 ± 0.7 mmol/L) for 24 h, followed by treatment with 4'-aminochalcones (250-7.81 µM). Cell viability was assessed by MTT assay. ROS were quantified by flow cytometry using DCFH-DA, while redox balance was evaluated through glutathione content and superoxide accumulation. The electronic properties of chalcone derivatives were further investigated by density functional theory calculations. The 4'-aminochalcones mitigate GM-induced oxidative stress in renal cells, and their antioxidant and cytoprotective activities are strongly influenced by electronic substituents. Electron-donating groups enhance reactivity, whereas electron-withdrawing groups improve safety, underscoring the importance of structure-effect relationships in the design of chalcone-based nephroprotective agents.","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The role of PDE6D in trafficking KRAS. PDE6D在贩运KRAS中的作用。

IF 2.5 4区生物学

Biological Chemistry Pub Date : 2026-04-21 Print Date: 2026-05-26 DOI: 10.1515/hsz-2026-0106

Luna Van Nimmen, Hanne Peeters, Shehab Ismail

引用次数: 0

CNKSR2 scaffold function in the mammalian nervous system. CNKSR2支架在哺乳动物神经系统中的功能。

IF 2.5 4区生物学

Biological Chemistry Pub Date : 2026-04-21 Print Date: 2026-07-24 DOI: 10.1515/hsz-2025-0241

Nils Rademacher, Poornima Anantha Subramanian, Sarah A Shoichet

{"title":"CNKSR2 scaffold function in the mammalian nervous system.","authors":"Nils Rademacher, Poornima Anantha Subramanian, Sarah A Shoichet","doi":"10.1515/hsz-2025-0241","DOIUrl":"10.1515/hsz-2025-0241","url":null,"abstract":"CNKSR proteins are multidomain scaffold proteins that coordinate protein complex formation and regulate intracellular signaling via diverse protein-protein interactions. Here, we focus on CNKSR2 (also known as CNK2 or MAGUIN), which is encoded by one of three vertebrate CNKSR genes that have undergone diversification and specification over the course of evolution, since the emergence of the earliest CNKSR-like modular proteins, which are observed already in the genome sequences of Porifera (sponges). The vertebrate CNKSR2 protein is unique in that it is the only CNKSR scaffold molecule with substantial expression in the central nervous system, and also the only CNKSR scaffold molecule for which there is a clear causal link to disease; patients with mutations that affect the function of the CNKSR2 protein suffer from a neurodevelopmental seizure disorder. For this reason in particular, understanding the cellular signalling cascades that are regulated by the CNKSR2 protein are of essential importance. In this review, we introduce the CNKSR proteins with their evolutionary trajectory, followed by an overview of available data on the vertebrate CNKSR2, with the aim to provide a concise summary of what is known about the expression and function of CNKSR2 in neurons of the central nervous system.","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":"159-168"},"PeriodicalIF":2.5,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147761024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Glue it together: self-assembly of the antibacterial GTPase GBP1. 粘在一起：抗菌GTPase GBP1的自组装。

IF 2.5 4区生物学

Biological Chemistry Pub Date : 2026-04-20 Print Date: 2026-05-26 DOI: 10.1515/hsz-2026-0112

Miriam Kutsch, Christian Herrmann

{"title":"Glue it together: self-assembly of the antibacterial GTPase GBP1.","authors":"Miriam Kutsch, Christian Herrmann","doi":"10.1515/hsz-2026-0112","DOIUrl":"10.1515/hsz-2026-0112","url":null,"abstract":"Guanylate-binding proteins (GBPs) are interferon-inducible large GTPases that play a central role in cell-autonomous immunity against intracellular bacterial pathogens. A defining feature of GBPs is their ability to translate GTP binding and hydrolysis into large-scale conformational rearrangements that drive self-assembly into higher-order structures, including dimers, polymers, and membrane-associated coatomers. This review integrates insights from biochemical, biophysical, structural, and cell biology studies to summarize current mechanistic models of GBP self-assembly, with a particular focus on human GBP1. We highlight how GTP hydrolysis-driven GBP1 polymers and coatomers act as self-regulating nanomachineries that recognize and remodel the pathogen-associated molecular pattern lipopolysaccharide, thereby fulfilling a dual function as immune sensor and effector in non-canonical inflammasome activation and bacterial membrane disruption. By directly linking nucleotide binding kinetics, enzymatic activity, and assembly dynamics to cellular and infection-related phenotypes, this review places decades of biochemical and biophysical work on GBP1 into a clear physiological context of antibacterial host defense.","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":"105-122"},"PeriodicalIF":2.5,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147761032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

GAP mimetic activity of pan-Ras TCI daraxonrasib synergizes with K-Ras Switch-II pocket inhibition. 泛ras TCI的GAP模拟活性与K-Ras开关- ii口袋抑制协同作用。

IF 2.5 4区生物学

Biological Chemistry Pub Date : 2026-04-17 Print Date: 2026-05-26 DOI: 10.1515/hsz-2025-0249

Patrick Pfaff, Kevan M Shokat

{"title":"GAP mimetic activity of pan-Ras TCI daraxonrasib synergizes with K-Ras Switch-II pocket inhibition.","authors":"Patrick Pfaff, Kevan M Shokat","doi":"10.1515/hsz-2025-0249","DOIUrl":"10.1515/hsz-2025-0249","url":null,"abstract":"Tricomplex inhibitors (TCIs) are a novel class of direct Ras inhibitors that target the GTP-bound Ras(on) state through recruitment of Cyclophilin A. Daraxonrasib (RMC-6236) is a pan-Ras TCI that was recently shown to restore GTPase activity of G12-mutant Ras proteins. Structural analysis of a pan-Ras TCI bound to K-Ras(GDP-AlF3) reveals a transition-state arrangement of Tyr32 and Gln61 that closely resembles endogenous GTPase-GAP complexes. This includes a closed Switch-I conformation engaging the cis-GTPase machinery in a manner analogous to non-arginine-finger GAPs such as RanGAP. These observations position pan-Ras TCIs as pharmacologic GAP mimetics. The GTPase-promoting activity of daraxonrasib suggests synergy with Switch-II pocket K-Ras inhibitors, including the approved GDP-state selective K-Ras G12C inhibitor adagrasib (MRTX-849), whose engagement of K-Ras(GTP) is kinetically constrained by slow endogenous hydrolysis of the mutant GTPase. We demonstrate that daraxonrasib sensitizes K-Ras(GTP) to adagrasib labeling in both recombinant protein and cellular contexts. In K-Ras G12C and G12D mutant cell lines, combinations of daraxonrasib with adagrasib or HRS-4642 (MRTX-1133 analog) yield more rapid K-Ras engagement, rapid p-ERK suppression, and significant Loewe synergy scores in viability assays. These findings establish GAP mimetics as rational and potent combination partners for Switch-II pocket inhibitors. The synergistic combination has potential to deepen and prolong pathway suppression while enabling dose reductions that may mitigate on-target toxicity and resistance.","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":"91-103"},"PeriodicalIF":2.5,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147761046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0