Biological Chemistry最新文献_第2页

The complex regulation of Slo1 potassium channels from a structural perspective 从结构角度看 Slo1 钾通道的复杂调控

IF 3.7 4区生物学

Biological Chemistry Pub Date : 2024-05-02 DOI: 10.1515/hsz-2024-0037

Tobias Raisch

{"title":"The complex regulation of Slo1 potassium channels from a structural perspective","authors":"Tobias Raisch","doi":"10.1515/hsz-2024-0037","DOIUrl":"https://doi.org/10.1515/hsz-2024-0037","url":null,"abstract":"Fast and regulated potassium efflux by Slo1 channels is crucial in many tissues in animals including neurons, the kidney and smooth muscle. During the last decade, structures have revealed many details about the gating mechanism and regulation of these large and complex molecular machines. This review summarizes these findings and the current knowledge about the intricate regulation of these important channels. Slo1 integrates sensing of the membrane potential via a voltage-sensor domain that undergoes subtle but significant structural rearrangements with a calcium-induced expansion of parts of the intracellular gating ring. Together, these two signals synergistically lead to changes in the conformation and chemical nature of the pore domain, allowing potassium ions to be translocated. In many native tissues, Slo1 channels are assembled with at least three classes of auxiliary subunits that change the gating kinetics or allow the channel to open also in absence of one of the two signals. Finally, Slo1 is inhibited, activated or deregulated by natural toxins and synthetic compounds, underlining the importance of the channel for the organism and as a potential target for drugs and other molecules.","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140836897","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

Unpaired cysteine insertions favor transmembrane dimerization and induce ligand-independent constitutive cytokine receptor signaling 非配对半胱氨酸插入有利于跨膜二聚化并诱导配体依赖性组成型细胞因子受体信号转导

IF 3.7 4区生物学

Biological Chemistry Pub Date : 2024-05-02 DOI: 10.1515/hsz-2023-0344

Lynn Affrica Felicitas Baumgärtner, Julia Ettich, Helene Balles, Dorothee Johanna Lapp, Sofie Mossner, Christin Bassenge, Meryem Ouzin, Helmut Hanenberg, Jürgen Scheller, Doreen Manuela Floss

{"title":"Unpaired cysteine insertions favor transmembrane dimerization and induce ligand-independent constitutive cytokine receptor signaling","authors":"Lynn Affrica Felicitas Baumgärtner, Julia Ettich, Helene Balles, Dorothee Johanna Lapp, Sofie Mossner, Christin Bassenge, Meryem Ouzin, Helmut Hanenberg, Jürgen Scheller, Doreen Manuela Floss","doi":"10.1515/hsz-2023-0344","DOIUrl":"https://doi.org/10.1515/hsz-2023-0344","url":null,"abstract":"Naturally occurring gain-of-function (GOF) mutants have been identified in patients for a variety of cytokine receptors. Although this constitutive activation of cytokine receptors is strongly associated with malignant disorders, ligand-independent receptor activation is also a useful tool in synthetic biology e.g. to improve adoptive cellular therapies with genetically modified T-cells. Balanced Interleukin (IL-)7 signaling via a heterodimer of IL-7 receptor (IL-7Rα) and the common γ-chain (γc) controls T- and B-cell development and expansion, whereas uncontrolled IL-7 signaling can drive acute lymphoid leukemia (ALL) development. The ALL-driver mutation PPCL in the transmembrane domain of IL-7Rα is a mutational insertion of the four amino acids proline-proline-cysteine-leucine and leads to ligand-independent receptor dimerization and constitutive activation. We showed here in the cytokine-dependent pre-B-cell line Ba/F3 that the PPCL-insertion in a synthetic version of the IL-7Rα induced γc-independent STAT5 and ERK phosphorylation and also proliferation of the cells and that booster-stimulation by arteficial ligands additionally generated non-canonical STAT3 phosphorylation via the synthetic IL-7Rα-PPCL-receptors. Transfer of the IL-7Rα transmembrane domain with the PPCL insertion into natural and synthetic cytokine receptor chains of the IL-6, IL-12 and Interferon families also resulted in constitutive receptor signaling. In conclusion, our data suggested that the insertion of the mutated PPCL IL-7Rα transmembrane domain is an universal approach to generate ligand-independent, constitutively active cytokine receptors.","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140836894","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

Advances in preclinical TCR characterization: leveraging cell avidity to identify functional TCRs 临床前 TCR 特征描述的进展：利用细胞亲和力识别功能性 TCR

IF 3.7 4区生物学

Biological Chemistry Pub Date : 2024-04-26 DOI: 10.1515/hsz-2023-0341

Andreas Carr, Laura M. Mateyka, Sebastian J. C. Scheu, Ana Bici, Joris Paijmans, Rogier M. Reijmers, Nina Dieminger, Shirin Dildebekova, Noomen Hamed, Karolin Wagner, Dirk H. Busch, Elvira D’Ippolito

{"title":"Advances in preclinical TCR characterization: leveraging cell avidity to identify functional TCRs","authors":"Andreas Carr, Laura M. Mateyka, Sebastian J. C. Scheu, Ana Bici, Joris Paijmans, Rogier M. Reijmers, Nina Dieminger, Shirin Dildebekova, Noomen Hamed, Karolin Wagner, Dirk H. Busch, Elvira D’Ippolito","doi":"10.1515/hsz-2023-0341","DOIUrl":"https://doi.org/10.1515/hsz-2023-0341","url":null,"abstract":"T-cell therapy has emerged as an effective approach for treating viral infections and cancers. However, a significant challenge is the selection of T-cell receptors (TCRs) that exhibit the desired functionality. Conventionally in vitro techniques, such as peptide sensitivity measurements and cytotoxicity assays, provide valuable insights into TCR potency but are labor-intensive. In contrast, measuring ligand binding properties (z-Movi technology) could provide an accelerated processing while showing robust correlations with T-cell functions. In this study, we assessed whether cell avidity can predict functionality also in the context of TCR-engineered T cells. To this end, we developed a flexible system for TCR re-expression by generating a Jurkat-derived T cell clone lacking TCR and CD3 expression through CRISPR-Cas9-mediated TRBC knockout. The knockin of a transgenic TCR into the TRAC locus restored TCR/CD3 expression, allowing for CD3-based purification of TCR-engineered T cells. Subsequently, we characterized these engineered cell lines by functional readouts, and assessment of binding properties through the z-Movi technology. Our findings revealed a strong correlation between the cell avidities and functional sensitivities of Jurkat TCR-T cells. Altogether, by integrating cell avidity measurements with our versatile T cell engineering platform, we established an accelerated system for enhancing the in vitro selection of clinically relevant TCRs.","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140798072","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

Structural homology of mite profilins to plant profilins is not indicative of allergic cross-reactivity. 螨虫廓清蛋白与植物廓清蛋白的结构同源性并不表明存在过敏性交叉反应。

IF 3.7 4区生物学

Biological Chemistry Pub Date : 2024-04-26 DOI: 10.1515/hsz-2023-0366

A. O'Malley, Sahana Sankaran, Avery Carriuolo, Kriti Khatri, Krzysztof Kowal, M. Chruszcz

引用次数: 0

Integrated machine learning and multimodal data fusion for patho-phenotypic feature recognition in iPSC models of dilated cardiomyopathy. 在扩张型心肌病的 iPSC 模型中集成机器学习和多模态数据融合，实现病理表型特征识别。

IF 3.7 4区生物学

Biological Chemistry Pub Date : 2024-04-24 DOI: 10.1515/hsz-2024-0023

Ruheen Wali, Hang Xu, Cleophas Cheruiyot, Hafiza Nosheen Saleem, Andreas Janshoff, Michael Habeck, A. Ebert

{"title":"Integrated machine learning and multimodal data fusion for patho-phenotypic feature recognition in iPSC models of dilated cardiomyopathy.","authors":"Ruheen Wali, Hang Xu, Cleophas Cheruiyot, Hafiza Nosheen Saleem, Andreas Janshoff, Michael Habeck, A. Ebert","doi":"10.1515/hsz-2024-0023","DOIUrl":"https://doi.org/10.1515/hsz-2024-0023","url":null,"abstract":"Integration of multiple data sources presents a challenge for accurate prediction of molecular patho-phenotypic features in automated analysis of data from human model systems. Here, we applied a machine learning-based data integration to distinguish patho-phenotypic features at the subcellular level for dilated cardiomyopathy (DCM). We employed a human induced pluripotent stem cell-derived cardiomyocyte (iPSC-CM) model of a DCM mutation in the sarcomere protein troponin T (TnT), TnT-R141W, compared to isogenic healthy (WT) control iPSC-CMs. We established a multimodal data fusion (MDF)-based analysis to integrate source datasets for Ca2+ transients, force measurements, and contractility recordings. Data were acquired for three additional layer types, single cells, cell monolayers, and 3D spheroid iPSC-CM models. For data analysis, numerical conversion as well as fusion of data from Ca2+ transients, force measurements, and contractility recordings, a non-negative blind deconvolution (NNBD)-based method was applied. Using an XGBoost algorithm, we found a high prediction accuracy for fused single cell, monolayer, and 3D spheroid iPSC-CM models (≥92 ± 0.08 %), as well as for fused Ca2+ transient, beating force, and contractility models (>96 ± 0.04 %). Integrating MDF and XGBoost provides a highly effective analysis tool for prediction of patho-phenotypic features in complex human disease models such as DCM iPSC-CMs.","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140661489","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

18β-glycyrrhetinic acid alleviates radiation-induced skin injury by activating the Nrf2/HO-1 signaling pathway 18β-甘草次酸通过激活 Nrf2/HO-1 信号通路减轻辐射引起的皮肤损伤

IF 3.7 4区生物学

Biological Chemistry Pub Date : 2024-04-10 DOI: 10.1515/hsz-2023-0200

Zeng Wang, Ruiqing Chen, Junying Chen, Li Su

引用次数: 0

Bovine ultralong CDR-H3 derived knob paratopes elicit potent TNF-α neutralization and enable the generation of novel adalimumab-based antibody architectures with augmented features. 牛超长CDR-H3衍生的旋钮副基团可产生强效的TNF-α中和作用，并能生成具有增强功能的新型阿达木单抗抗体结构。

IF 2.9 4区生物学

Biological Chemistry Pub Date : 2024-02-20 Print Date: 2024-07-26 DOI: 10.1515/hsz-2023-0370

Paul Arras, Jasmin Zimmermann, Britta Lipinski, Bernhard Valldorf, Andreas Evers, Desislava Elter, Simon Krah, Achim Doerner, Enrico Guarnera, Vanessa Siegmund, Harald Kolmar, Lukas Pekar, Stefan Zielonka

引用次数: 0

Celastrol inhibits angiogenesis and the biological processes of MDA-MB-231 cells via the DEGS1/S1P signaling pathway Celastrol 通过 DEGS1/S1P 信号通路抑制血管生成和 MDA-MB-231 细胞的生物过程

IF 3.7 4区生物学

Biological Chemistry Pub Date : 2023-12-11 DOI: 10.1515/hsz-2023-0324

Lulu Jia, Shengnan Zhu, Mingfei Zhu, Rongrong Nie, Lingyue Huang, Siyuan Xu, Yuqin Luo, Huazhen Su, Shaoyuan Huang, Qinyou Tan

{"title":"Celastrol inhibits angiogenesis and the biological processes of MDA-MB-231 cells via the DEGS1/S1P signaling pathway","authors":"Lulu Jia, Shengnan Zhu, Mingfei Zhu, Rongrong Nie, Lingyue Huang, Siyuan Xu, Yuqin Luo, Huazhen Su, Shaoyuan Huang, Qinyou Tan","doi":"10.1515/hsz-2023-0324","DOIUrl":"https://doi.org/10.1515/hsz-2023-0324","url":null,"abstract":"Celastrol (Cel) shows potent antitumor activity in various experimental models. This study examined the relationship between Cel’s antivascular and antitumor effects and sphingolipids. CCK-8 assay, transwell assay, Matrigel, PCR-array/RT-PCR/western blotting/immunohistochemistry assay, ELISA and HE staining were used to detect cell proliferation, migration and invasion, adhesion and angiogenesis, mRNA and protein expression, S1P production and tumor morphology. The results showed that Cel could inhibit proliferation, migration or invasion, adhesion and angiogenesis of human umbilical vein endothelial cells (HUVECs) and MDA-MB-231 cells by downregulating the expression of degenerative spermatocyte homolog 1 (DEGS1). Transfection experiments showed that downregulation of DEGS1 inhibited the above processes and sphingosine-1-phosphate (S1P) production of HUVECs and MDA-MB-231 cells, while upregulation of DEGS1 had the opposite effects. Coculture experiments showed that HUVECs could promote proliferation, migration and invasion of MDA-MB-231 cells through S1P/sphingosine-1-phosphate receptor (S1PR) signaling pathway, while Cel inhibited these processes in MDA-MB-231 cells induced by HUVECs. Animal experiments showed that Cel could inhibit tumor growth in nude mice. Western blotting, immunohistochemistry and ELISA assay showed that Cel downregulated the expression of DEGS1, CD146, S1PR1-3 and S1P production. These data confirm that DEGS1/S1P signaling pathway may be related to the antivascular and antitumor effects of cel.","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2023-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138572049","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: Horizons in Neuroscience - Organoids, Optogenetics and Remote Control. 亮点:神经科学的视野-类器官，光遗传学和远程控制。

IF 3.7 4区生物学

Biological Chemistry Pub Date : 2023-11-27 Print Date: 2024-01-29 DOI: 10.1515/hsz-2023-0343

Rolf Heumann

引用次数: 0

Visualization of the membrane surface and cytoskeleton of oligodendrocyte progenitor cell growth cones using a combination of scanning ion conductance and four times expansion microscopy. 利用扫描离子电导和四倍扩增显微镜观察少突胶质祖细胞生长锥的膜表面和细胞骨架。

IF 3.7 4区生物学

Biological Chemistry Pub Date : 2023-11-13 Print Date: 2024-01-29 DOI: 10.1515/hsz-2023-0217

Annika Haak, Heiko M Lesslich, Irmgard D Dietzel

{"title":"Visualization of the membrane surface and cytoskeleton of oligodendrocyte progenitor cell growth cones using a combination of scanning ion conductance and four times expansion microscopy.","authors":"Annika Haak, Heiko M Lesslich, Irmgard D Dietzel","doi":"10.1515/hsz-2023-0217","DOIUrl":"10.1515/hsz-2023-0217","url":null,"abstract":"<p><p>Growth cones of oligodendrocyte progenitor cells (OPCs) are challenging to investigate with conventional light microscopy due to their small size. Especially substructures such as filopodia, lamellipodia and their underlying cytoskeleton are difficult to resolve with diffraction limited microscopy. Light microscopy techniques, which surpass the diffraction limit such as stimulated emission depletion microscopy, often require expensive setups and specially trained personnel rendering them inaccessible to smaller research groups. Lately, the invention of expansion microscopy (ExM) has enabled super-resolution imaging with any light microscope without the need for additional equipment. Apart from the necessary resolution, investigating OPC growth cones comes with another challenge: Imaging the topography of membranes, especially label- and contact-free, is only possible with very few microscopy techniques one of them being scanning ion conductance microscopy (SICM). We here present a new imaging workflow combining SICM and ExM, which enables the visualization of OPC growth cone nanostructures. We correlated SICM recordings and ExM images of OPC growth cones captured with a conventional widefield microscope. This enabled the visualization of the growth cones' membrane topography as well as their underlying actin and tubulin cytoskeleton.</p>","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2023-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89716832","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