The complex regulation of Slo1 potassium channels from a structural perspective
Biol Chem. 2024 May 3. doi: 10.1515/hsz-2024-0037. Online ahead of print.ABSTRACTFast 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 rearran...
Source: Biological Chemistry - May 2, 2024 Category: Chemistry Authors: Tobias Raisch Source Type: research

Unpaired cysteine insertions favor transmembrane dimerization and induce ligand-independent constitutive cytokine 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.PMID:38695485 | DOI:10.1515/hsz-2023-0344 (Source: Biological Chemistry)
Source: Biological Chemistry - May 2, 2024 Category: Chemistry Authors: Lynn Affrica Felicitas Baumg ärtner Julia Ettich Helene Balles Dorothee Johanna Lapp Sofie Mossner Christin Bassenge Meryem Ouzin Helmut Hanenberg J ürgen Scheller Doreen Manuela Floss Source Type: research

Advances in preclinical TCR characterization: leveraging cell avidity to identify functional TCRs
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 stron...
Source: Biological Chemistry - April 26, 2024 Category: Chemistry 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 Source Type: research

Structural homology of mite profilins to plant profilins is not indicative of allergic cross-reactivity
Biol Chem. 2024 Apr 26. doi: 10.1515/hsz-2023-0366. Online ahead of print.ABSTRACTStructural and allergenic characterization of mite profilins has not been previously pursued to a similar extent as plant profilins. Here, we describe structures of profilins originating from Tyrophagus putrescentiae (registered allergen Tyr p 36.0101) and Dermatophagoides pteronyssinus (here termed Der p profilin), which are the first structures of profilins from Arachnida. Additionally, the thermal stabilities of mite and plant profilins are compared, suggesting that the high number of cysteine residues in mite profilins may play a role in ...
Source: Biological Chemistry - April 25, 2024 Category: Chemistry Authors: Andrea O'Malley Sahana Sankaran Avery Carriuolo Kriti Khatri Krzysztof Kowal Maksymilian Chruszcz Source Type: research

Integrated machine learning and multimodal data fusion for patho-phenotypic feature recognition in iPSC models of dilated cardiomyopathy
Biol Chem. 2024 Apr 24. doi: 10.1515/hsz-2024-0023. Online ahead of print.ABSTRACTIntegration 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. ...
Source: Biological Chemistry - April 23, 2024 Category: Chemistry Authors: Ruheen Wali Hang Xu Cleophas Cheruiyot Hafiza Nosheen Saleem Andreas Janshoff Michael Habeck Antje Ebert Source Type: research

18 β-glycyrrhetinic acid alleviates radiation-induced skin injury by activating the Nrf2/HO-1 signaling pathway
In conclusion, our results suggest that 18β-GA reduces intracellular ROS production and apoptosis by activating the Nrf2/HO-1 signaling pathway, leading to amelioration of radiation dermatitis.PMID:38598859 | DOI:10.1515/hsz-2023-0200 (Source: Biological Chemistry)
Source: Biological Chemistry - April 10, 2024 Category: Chemistry Authors: Zeng Wang Ruiqing Chen Junying Chen Li Su Source Type: research