Biological Chemistry最新文献_第2页

Structure of astacin and the discovery of metzincins. 阿沙星的结构与甲津素的发现。

IF 2.5 4区生物学

Biological Chemistry Pub Date : 2026-08-19 DOI: 10.1515/hsz-2026-0142

F Xavier Gomis-Rüth, Walter Stöcker

引用次数: 0

Unmasking the modified small non-coding RNome: detection strategies for RNA modifications. 揭示修饰的小非编码RNome: RNA修饰的检测策略。

IF 2.5 4区生物学

Biological Chemistry Pub Date : 2026-08-18 DOI: 10.1515/hsz-2026-0148

Bennett Henzeler, Kathrin Halter, Özge Simsir, Pascal Giehr, Sabine Schneider

{"title":"Unmasking the modified small non-coding RNome: detection strategies for RNA modifications.","authors":"Bennett Henzeler, Kathrin Halter, Özge Simsir, Pascal Giehr, Sabine Schneider","doi":"10.1515/hsz-2026-0148","DOIUrl":"https://doi.org/10.1515/hsz-2026-0148","url":null,"abstract":"RNA molecules carry a wide range of chemical modifications that play key roles in regulating their structure, stability, and function. These modifications are especially abundant in small and non-coding RNAs, such as transfer RNAs (tRNA), ribosomal RNA (rRNA), and related fragments, where they influence processes from translation to gene silencing. However, studying these modifications remains challenging due to the short length of these RNAs, their strong secondary structures, and the high density of chemical marks, all of which can interfere with standard sequencing workflows. This review summarizes current strategies for detecting and mapping RNA modifications in the small RNome. We outline the diversity of RNA classes and their characteristic modification patterns, and then discuss key methodological advances. These include demodification-based sequencing approaches for heavily modified RNAs, targeted chemical and enzymatic methods for site-specific mapping, and emerging direct RNA sequencing technologies that allow analysis of native molecules without prior conversion. We also highlight orthogonal validation techniques used to confirm modification identity and improve reliability. Together, these approaches provide complementary insights, but no single method is sufficient on its own. Careful experimental design and validation therefore remain essential for accurate and comprehensive analysis of RNA modifications.","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148757175","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

PLPPR3 and the making of neuronal filopodia. PLPPR3与神经元丝状足的形成。

IF 2.5 4区生物学

Biological Chemistry Pub Date : 2026-08-13 DOI: 10.1515/hsz-2026-0119

Thomas J Böddeker, George Leondaritis, Britta J Eickholt

引用次数: 0

Timing the origin: chromatin, transcription, and the spatiotemporal control of eukaryotic DNA replication. 起源时间：真核生物DNA复制的染色质、转录和时空控制。

IF 2.5 4区生物学

Biological Chemistry Pub Date : 2026-08-13 DOI: 10.1515/hsz-2026-0167

Anne Soeding, Lia Willerding, Lea Riemann, L Maximilian Reuter

{"title":"Timing the origin: chromatin, transcription, and the spatiotemporal control of eukaryotic DNA replication.","authors":"Anne Soeding, Lia Willerding, Lea Riemann, L Maximilian Reuter","doi":"10.1515/hsz-2026-0167","DOIUrl":"10.1515/hsz-2026-0167","url":null,"abstract":"The eukaryotic genome is replicated according to a tightly regulated temporal program that ensures each DNA segment is copied once per cell cycle. This program reflects the coordinated action of replication origin licensing, chromatin state, transcriptional activity, and nuclear organisation. While the core mechanisms of licensing and initiation are well characterised, the determinants of origin selection and firing time remain incompletely understood. In budding yeast, origins are defined by specific DNA elements and chromatin features, whereas in metazoans, origin specification is largely sequence-independent and influenced by epigenetic and three-dimensional genome architecture. This review summarises current knowledge of how replication timing is established, regulated, and functionally integrated with chromatin states across eukaryotes, with emphasis on chromatin accessibility, histone modifications and variants, transcriptional regulators, and higher-order genome topology. It also highlights recent genome-wide approaches that map origin licensing, usage, and nascent DNA synthesis at high resolution, revealing dynamic connections between replication, transcription, and nuclear compartmentalisation. Finally, we discuss how disrupted replication timing contributes to replication stress, genome instability, ageing, and cancer. By integrating findings from diverse eukaryotic systems, this provides an updated framework for understanding replication timing as a key layer of genome regulation.","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148722092","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

Glucocorticoid receptor biology through the omics lens: context matters. 糖皮质激素受体生物学通过组学镜头：环境问题。

IF 2.5 4区生物学

Biological Chemistry Pub Date : 2026-08-13 DOI: 10.1515/hsz-2026-0147

Priya Singh, Franziska Greulich

{"title":"Glucocorticoid receptor biology through the omics lens: context matters.","authors":"Priya Singh, Franziska Greulich","doi":"10.1515/hsz-2026-0147","DOIUrl":"10.1515/hsz-2026-0147","url":null,"abstract":"Over the past two decades, advances in omics technologies, combined with classical genetics, have fundamentally reshaped our understanding of glucocorticoid (GC) biology and informed strategies to optimise GC therapy. Traditional models focused on uniform, ligand-dependent gene regulation via the glucocorticoid receptor (GR). In contrast, genome-wide transcriptomic, epigenomic, and proteomic approaches have revealed a far more complex landscape in which GC responses are highly cell-type-specific and context-dependent. High-resolution transcriptomics and single-cell RNA sequencing have uncovered divergent GC-regulated gene networks across immune, metabolic, and structural cell lineages, providing mechanistic insight into both therapeutic efficacy and tissue-specific adverse effects. Epigenomic profiling, including ChIP-seq and ATAC-seq, has shown that chromatin accessibility, enhancer architecture, and GR cistromes vary across cell types and states, thereby shaping transcriptional outcomes. Complementary proteomic studies have defined GR-interacting protein networks that modulate receptor activity. Together, these multi-layered datasets support a systems-level model of GR signalling that integrates chromatin context, transcriptional regulation, and cellular state and begins to explain GC sensitivity, resistance, and context-specific side effects. Emerging multi-omics and single-cell multimodal approaches now enable high-resolution dissection of GC action in complex tissues and disease contexts, advancing precision therapeutic strategies.","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148720042","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

Functional interaction of HINT1 with MRTF-A: complex formation, protein stabilisation and transcriptional repression. HINT1与MRTF-A的功能相互作用：复合物的形成、蛋白稳定和转录抑制。

IF 2.5 4区生物学

Biological Chemistry Pub Date : 2026-08-05 DOI: 10.1515/hsz-2026-0143

Marianne Stognienko, Guido Posern

{"title":"Functional interaction of HINT1 with MRTF-A: complex formation, protein stabilisation and transcriptional repression.","authors":"Marianne Stognienko, Guido Posern","doi":"10.1515/hsz-2026-0143","DOIUrl":"https://doi.org/10.1515/hsz-2026-0143","url":null,"abstract":"Histidine triad nucleotide-binding protein 1 (HINT1) is a small and evolutionarily conserved HIT family protein with putative tumor suppressor function. It has been implicated in the negative regulation of several transcription factors, but a role for HINT1 in Myocardin-related transcription factor A (MRTF-A)/serum response factor (SRF) signaling has not been described. Here, we examined whether HINT1 functionally interacts with MRTF-A in fibroblasts. HINT1 reduced MRTF-A-dependent reporter activity in a dose-dependent manner, whereas a histidine triad mutant did not. Repression by HINT1 was retained upon deletion of the N-terminal RPEL motifs of MRTF-A, indicating that the effect was not confined to the inhibition of Rho-actin signaling. In parallel, HINT1-WT increased the MRTF-A protein abundance, which required the C-terminal part of MRTF-A. Co-immunoprecipitation experiments revealed the physical association of HINT1 with MRTF-A, whereas the histidine triad mutant or a C-terminally truncated MRTF-A did not show complex formation. Thus, our work suggests that HINT1 acts as a negative regulator of MRTF-A-dependent transcription by binding to the MRTF-A C-terminal part, which appears to require the histidine triad region and is accompanied by a separable increase in MRTF-A abundance.","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148700743","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

Highlight: scaffolding of membrane-proximal processes. 亮点：近端膜突支架。

IF 2.5 4区生物学

Biological Chemistry Pub Date : 2026-07-27 Print Date: 2026-07-24 DOI: 10.1515/hsz-2026-0171

Tanja Maritzen, Volker Haucke

引用次数: 0

Learning from trypsin(ogen) structures: conformational flexibility and functional disorder. 从胰蛋白酶（原）结构中学习：构象灵活性和功能紊乱。

IF 2.5 4区生物学

Biological Chemistry Pub Date : 2026-07-20 DOI: 10.1515/hsz-2026-0139

Milton T Stubbs

{"title":"Learning from trypsin(ogen) structures: conformational flexibility and functional disorder.","authors":"Milton T Stubbs","doi":"10.1515/hsz-2026-0139","DOIUrl":"https://doi.org/10.1515/hsz-2026-0139","url":null,"abstract":"Our understanding of trypsin, its zymogenicity and its inhibition is intimately intertwined with the history of biochemistry. Early structural studies revealed its close relationship to chymotrypsin, with its active site triad, oxyanion hole and N-terminus involved in a buried salt bridge near the active site. Its complex with basic pancreatic trypsin inhibitor provided a model for how peptide substrates bind to and are cleaved by the proteinase. Analysis of crystals of trypsinogen by Wolfram Bode and Robert Huber revealed that a large region of the zymogen is disordered prior to proteolytic activation, with an associated disruption of the oxyanion hole and substrate binding pockets, highlighting the importance of disorder in protein function. As archetype of numerous therapeutically important serine proteinases, trypsin can also serve as a surrogate for structure-based drug design. Trypsin variants designed for ligand binding studies resulted however in an unexpected plasticity of the mutant proteins that underlines the complexity of protein stability. A trypsin variant selected for peptide ligation (reverse proteolysis) was shown to possess zymogen-like characteristics that proved central to its application in modification of therapeutic proteins. The review pays homage to the seminal works of Bode and Huber and their influence on modern structural biology.","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148468780","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

On the structure and function of granzymes, the deadly squad of cytotoxic lymphocytes. 细胞毒性淋巴细胞的致命小组颗粒酶的结构和功能。

IF 2.5 4区生物学

Biological Chemistry Pub Date : 2026-07-14 DOI: 10.1515/hsz-2025-0251

José Luis Gardeazábal-Torbado, Eva Estébanez-Perpiñá, Pablo Fuentes-Prior

{"title":"On the structure and function of granzymes, the deadly squad of cytotoxic lymphocytes.","authors":"José Luis Gardeazábal-Torbado, Eva Estébanez-Perpiñá, Pablo Fuentes-Prior","doi":"10.1515/hsz-2025-0251","DOIUrl":"https://doi.org/10.1515/hsz-2025-0251","url":null,"abstract":"Granzymes are a family of trypsin-like serine proteinases (TLSP) produced by cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. They play critical roles in immune defense by inducing diverse forms of programmed cell death (e.g., apoptosis, pyroptosis, and necroptosis) in infected or abnormal cells. Here, we review current information on the structural mechanisms underlying the activation, substrate specificity, and inhibition of the five human granzymes (GzmA, GzmB, GzmH, GzmK, and GzmM). We highlight how specific variations of the canonical trypsin fold allow these five proteinases to display entirely distinct substrate specificities. We emphasize the role of allosteric mechanisms, such as exosites and dimerization, in expanding their substrate recognition profiles far beyond simple P1 cleavage site requirements. We discuss the rapidly growing evidence on the contribution of dysregulated granzyme activity to various inflammatory and autoimmune diseases. Finally, we explore emerging therapeutic strategies targeting granzymes, aiming to either enhance their beneficial cytotoxic effects (e.g., in cancer immunotherapy and infection) or inhibit their pathological roles in chronic inflammation and autoimmunity. Despite significant progress, open questions remain regarding the full spectrum of physiological granzyme substrates, their precise synergistic actions in vivo, and the translational challenges of applying in vitro findings to complex clinical contexts.","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148429731","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

IF 2.5 4区生物学

Biological Chemistry Pub Date : 2026-07-14 DOI: 10.1515/hsz-2026-0156

Abdul Rahman, Anja Marquardt, Johannes N Greve

{"title":"Actin-related and actin-like proteins: functional diversification of the actin-fold.","authors":"Abdul Rahman, Anja Marquardt, Johannes N Greve","doi":"10.1515/hsz-2026-0156","DOIUrl":"https://doi.org/10.1515/hsz-2026-0156","url":null,"abstract":"Actin-related proteins (Arps) and actin-like proteins constitute a subfamily of actin-fold proteins that are evolutionarily and structurally related to conventional actin but functionally distinct. While actin is defined by its ability to form dynamic filaments, bind and hydrolyze ATP, and serve as a major cytoskeletal scaffold, Arps and actin-like proteins have evolved specialized roles in cytoplasmic and nuclear protein complexes. The Arp2/3 complex mediates branched actin nucleation, whereas the dynactin complex, containing Arp1 and Arp11, functions as an activator and cargo-adaptor for dynein-dependent intracellular transport. In the nucleus, multiple Arps, actin, and actin-like proteins are incorporated into large ATP-dependent chromatin-remodelling and histone-modifying complexes, where they regulate nucleosome positioning, histone variant exchange, and transcriptional accessibility. Beyond canonical Arps, mammals encode a range of non-canonical Arps and actin-like proteins, many of which exhibit tissue-specific expression, particularly in the testis, and are associated with spermiogenesis and male fertility. This review summarizes the current knowledge on the classification, structure-function relationship, and cellular roles of human Arps and actin-like proteins, as well as their links to human disease, including immunodeficiency, neurodevelopmental disorders, infertility, and cancer.","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148429726","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