{"title":"The 76th Mosbacher Colloquium: AI-driven (r)evolution in structural biology and protein design.","authors":"Birte Höcker, Ina Koch, Janosch Hennig","doi":"10.1515/hsz-2025-0184","DOIUrl":"https://doi.org/10.1515/hsz-2025-0184","url":null,"abstract":"<p><p>The 76th Mosbacher Kolloquium focused on recent advances in machine learning applications for structural biology and protein design. It covered topics spanning artificial intelligence-driven protein structure prediction, integrative modeling, generative protein design, and general applications in life sciences. With strong participation, high-caliber talks, and a clear focus on the integration of AI in biomolecular research, the meeting underscored the transformative role of machine learning in molecular biosciences and provided a vibrant platform for knowledge exchange across disciplines and generations.</p>","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184512","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}
{"title":"Manipulating mitochondrial gene expression.","authors":"Drishan Dahal, Luis D Cruz-Zargoza, Peter Rehling","doi":"10.1515/hsz-2025-0170","DOIUrl":"https://doi.org/10.1515/hsz-2025-0170","url":null,"abstract":"<p><p>Mitochondria are essential for cellular metabolism, serving as the primary source of adenosine triphosphate (ATP). This energy is generated by the oxidative phosphorylation (OXPHOS) system located in the inner mitochondrial membrane. Impairments in this machinery are linked to serious human diseases, especially in tissues with high energy demands. Assembly of the OXPHOS system requires the coordinated expression of genes encoded by both the nuclear and mitochondrial genomes. The mitochondrial DNA encodes for 13 protein components, which are synthesized by mitochondrial ribosomes and inserted into the inner membrane during translation. Despite progress, key aspects of how mitochondrial gene expression is regulated remain elusive, largely due to the organelle's limited genetic accessibility. However, emerging technologies now offer new tools to manipulate various stages of this process. In this review, we explore recent strategies that expand our ability to target mitochondria genetically.</p>","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085088","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}
{"title":"Conserved function, divergent evolution: mitochondrial outer membrane insertases across eukaryotes.","authors":"Anna Roza Dimogkioka, Doron Rapaport","doi":"10.1515/hsz-2025-0169","DOIUrl":"https://doi.org/10.1515/hsz-2025-0169","url":null,"abstract":"<p><p>Mitochondrial function relies heavily on the proper targeting and insertion of nuclear-encoded proteins into the outer mitochondrial membrane (OMM), a process mediated by specialised biogenesis factors known as insertases. These insertases are essential for the membrane integration of α-helical OMM proteins, which contain one or multiple hydrophobic transmembrane segments. While the general mechanisms of mitochondrial protein import are well established, recent research has shed light on the diversity and evolutionary conservation of OMM insertases across eukaryotic lineages. In <i>Saccharomyces cerevisiae</i>, the mitochondrial import (MIM) complex, composed of Mim1 and Mim2, facilitates the integration of various α-helical OMM proteins, often in cooperation with import receptors such as Tom20 and Tom70. In <i>Trypanosoma brucei</i>, the functional MIM counterpart pATOM36 performs a similar role despite lacking sequence and structural homology, reflecting a case of convergent evolution. In mammals, MTCH2 has emerged as the principal OMM insertase, with MTCH1 playing a secondary, partially redundant role. This review provides a comparative analysis of these insertases, emphasising their conserved functionality, species-specific adaptations, and mechanistic nuances.</p>","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144803360","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}
{"title":"Biogenesis and function of the mitochondrial solute carrier (SLC25) family in yeast.","authors":"Celina Nauerz, Ophry Pines, Johannes M Herrmann","doi":"10.1515/hsz-2025-0152","DOIUrl":"https://doi.org/10.1515/hsz-2025-0152","url":null,"abstract":"<p><p>The mitochondrial solute carrier family, also called SLC25 family, comprises a group of structurally and evolutionary related transporters that are embedded in the mitochondrial inner membrane. About 35 and 53 mitochondrial carrier proteins are known in yeast and human cells, respectively, which transport nucleotides, metabolites, amino acids, fatty acids, inorganic ions and cofactors across the inner membrane. They are proposed to function by a common rocker-switch mechanism, alternating between conformations that expose substrate-binding pockets to the intermembrane space (cytoplasmic state) and to the matrix (matrix state). The substrate specificities of both states differ so that carriers can operate as antiporters, symporters or uniporters. Carrier proteins share a characteristic structure comprising six transmembrane domains and expose both termini to the intermembrane space. Most carriers lack N-terminal presequences but use carrier-specific internal targeting signals that direct them into mitochondria via a specific import route, known as the 'carrier pathway'. Owing to their hydrophobicity and aggregation-prone nature, the mistargeting of carriers can lead to severe proteotoxic stress and diseases. In this review article, we provide an overview about the structure, biogenesis and physiology of carrier proteins, focusing on baker's yeast where their biology is particularly well characterized.</p>","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144940948","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}
Biological ChemistryPub Date : 2025-06-17Print Date: 2025-03-26DOI: 10.1515/hsz-2024-0159
Alexander Gast, Sebastian Schreiber, Joachim Jose
{"title":"Rapid method for evaluation of CK2 enzymatic activity and CK2α/CK2β-interaction in <i>Escherichia coli</i> cell lysates.","authors":"Alexander Gast, Sebastian Schreiber, Joachim Jose","doi":"10.1515/hsz-2024-0159","DOIUrl":"10.1515/hsz-2024-0159","url":null,"abstract":"<p><p>This study introduces a novel, rapid assay to measure CK2α activity in <i>Escherichia coli</i> cell lysates. By fusing CK2α with the fluorescent protein mScarlet it was possible to quantify CK2α concentration directly in lysates. We used the dose-dependent increase of CK2α activity after addition of CK2β<sup>1-193</sup> to determine the dissociation constants (<i>K</i> <sub><i>D</i></sub> ) of the CK2α/CK2β-interaction. As a first trial, activity and affinity of the variant CK2α<sup>R191Q</sup> to CK2β<sup>1-193</sup> was investigated using the developed assays. This mutation in the <i>CSNK2A1</i> gene, encoding CK2α is related to the Okur-Chung Neurodevelopmental Syndrome (OCNDS). Apparent <i>K</i> <sub><i>D</i></sub> values of 13 nM for the CK2α<sup>R191Q</sup>/CK2β interaction and 7.4 nM for the CK2α/CK2β interaction were determined using nonlinear regression. Uncertainties with regards to the concentration of both binding partners were propagated through the entire process of nonlinear regression by Monte Carlo simulations. This way, accuracy confidence intervals of the <i>K</i> <sub><i>D</i></sub> -values were derived. This resulted in 96.4 % confidence that the accurate <i>K</i> <sub><i>D</i></sub> -values of the CK2α-CK2β and CK2α<sup>R191Q</sup>-CK2β interactions were different. The results suggest potential disruptions in oligomeric assembly caused by the R191Q mutation.</p>","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":"406 3-4","pages":"117-124"},"PeriodicalIF":2.4,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144641705","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}
Janis Hoetzel, Cristina Bofill-Bosch, Andres W Martinez, Martin M Rudolph, Florian Groher, Beatrix Suess
{"title":"Triple SELEX approach for the selection of a highly specific RNA aptamer binding homoeriodictyol.","authors":"Janis Hoetzel, Cristina Bofill-Bosch, Andres W Martinez, Martin M Rudolph, Florian Groher, Beatrix Suess","doi":"10.1515/hsz-2025-0118","DOIUrl":"https://doi.org/10.1515/hsz-2025-0118","url":null,"abstract":"<p><p>The application of synthetic riboswitches or aptamer-based biosensors for the monitoring of engineered metabolic pathways greatly depends on a high degree of target molecule specificity. Since metabolic pathways include close derivatives that often differ only in single moieties, the binding specificity of aptamers utilized for these systems has to be high. In the present study, we selected an RNA aptamer that is highly specific in its binding to homoeriodictyol while discriminating its close derivatives eriodictyol and naringenin. This high degree in specificity was achieved through three consecutive SELEX approaches while the selection parameters were adjusted and refined from one to the next. The adjustments along the process, with the selection outcome and next-generation sequencing analysis of the selection rounds, led to valuable insights into the stringency necessary to facilitate target specificity in aptamers obtained from SELEX. From the third selection, we obtained a highly binding specific aptamer and examined its structure and binding properties. Overall, our results connect the importance of selection stringency with SELEX outcome and aptamer specificity while providing a highly selective, homoeriodictyol-binding RNA aptamer.</p>","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144214724","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}
Biological ChemistryPub Date : 2025-06-03Print Date: 2025-03-26DOI: 10.1515/hsz-2025-0147
Karsten Niefind, Claudia Götz, Joachim Jose
{"title":"70 years of CK2: still exciting, essential - and enigmatic!","authors":"Karsten Niefind, Claudia Götz, Joachim Jose","doi":"10.1515/hsz-2025-0147","DOIUrl":"10.1515/hsz-2025-0147","url":null,"abstract":"","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":"65-67"},"PeriodicalIF":2.9,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144214723","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}
{"title":"TBK1 alleviates triptolide-induced nephrotoxic injury by up-regulating mitophagy in HK2 cells.","authors":"Xinxin Lu, Qionghui Huang, Zhaohui He, Huanjie Zhou, Zhenwei Chen, Youjian Zhou, Tiecheng Yang, Lang-Jing Zhu","doi":"10.1515/hsz-2024-0141","DOIUrl":"https://doi.org/10.1515/hsz-2024-0141","url":null,"abstract":"<p><p><i>Tripterygium wilfordii</i> has been used for a long time to treat autoimmune diseases. Its toxic side effects limit its clinical application. Mitophagy plays a protective role in various diseases. TANK-binding kinase 1 (TBK1) is a mitophagy-promoting molecule. This study aimed to investigate whether TBK1 could alleviate triptolide (TP)-induced nephrotoxicity by regulating mitophagy. To establish TP-induced nephrotoxic injury in animal model, 16 Sprague-Dawley rats were administered with TP by gavage, then renal tissues were collected for hematoxylin and eosin (HE) staining, western blotting and immunofluorescence analysis. To investigate whether up-regulation of TBK1 could alleviate TP-induced nephrotoxic injury and the specific mechanism, HK-2 cells were cultured <i>in vitro</i>, transfected with TBK1-overexpression recombinant lentivirus, then treated with TP. Western blotting, immunofluorescence, flow cytometry, multifunctional microplate detector were used to detect the relevant molecules. Here we found that TP caused kidney function damage, declined mitophagy levels, decreased the expression of TBK1 and mitophagy-related proteins in rats. TP stimulation decreased cell viability, mitochondrial membrane potential, mitophagy-protein, the formation of mito-autophagosomes and mito-autophagolysosomes in HK-2 cells. Upregulating TBK1 could reverse these damages. In summary, TP-induced cell injury had decreased mitophagy levels. Up-regulating TBK1 could increase mitophagy and further alleviate TP-induced cell injury.</p>","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143960337","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}
Biological ChemistryPub Date : 2025-05-05Print Date: 2025-03-26DOI: 10.1515/hsz-2024-0150
Apurva T Prabhakar, Iain M Morgan
{"title":"CK2 control of human papillomavirus life cycles.","authors":"Apurva T Prabhakar, Iain M Morgan","doi":"10.1515/hsz-2024-0150","DOIUrl":"10.1515/hsz-2024-0150","url":null,"abstract":"<p><p>Human papillomaviruses are causative agents in around 5 % of all cancers, and in a number of other human diseases. While prophylactic vaccines will alleviate the HPV disease burden on future generations, there are currently no therapeutic anti-viral strategies for combating HPV infections or lesions. HPV induce the proliferation of infected epithelial cells and modulate the host differentiation response, and both of these controls are required for a successful viral life cycle. Enhanced understanding of viral-host interactions during the viral life cycle will identify potential novel anti-viral strategies for therapeutic development. This minireview will summarize the critical role of the host enzyme CK2 in regulating the function of the viral proteins E1, E2 and E7; such control makes CK2 a critical enzyme for regulating HPV life cycles. Therapeutic strategies blocking CK2 function to combat HPV infections and treat HPV diseases will be described.</p>","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":"81-88"},"PeriodicalIF":2.4,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143973617","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}
Biological ChemistryPub Date : 2025-05-05Print Date: 2025-03-26DOI: 10.1515/hsz-2024-0162
Hanna Kavaliova, Barbara Lecis, Demetra Ballardin, Laetitia Cobret, Thierry Bienvenu, Severine Morisset-Lopez, Heike Rebholz
{"title":"Pathogenic missense variants of CSNK2B associated with Poirier-Bienvenu neurodevelopmental disorder impact differently on CK2 holoenzyme formation.","authors":"Hanna Kavaliova, Barbara Lecis, Demetra Ballardin, Laetitia Cobret, Thierry Bienvenu, Severine Morisset-Lopez, Heike Rebholz","doi":"10.1515/hsz-2024-0162","DOIUrl":"10.1515/hsz-2024-0162","url":null,"abstract":"<p><p>Poirier-Bienvenu neurodevelopmental syndrome is a neurodevelopmental disorder associated with <i>de novo</i> variants of the <i>CSNK2B</i> gene, characterized by intellectual disability, developmental delay, frequent seizures and more. While the majority of variants are nonsense variants leading to abortion of protein translation and no or truncated CK2β, many pathogenic missense variants also exist. We investigated the effect of four variants on CK2 holoenzyme formation and activity. We show that variants in the Zinc-finger region leads to reduced protein stability and altered subcellular localization. The instability is partly mediated by proteasomal and lysosomal degradation. We further show that homodimerization of these CK2β variants (p.Arg111Pro, p.Cys137Phe), localized within the Zinc-finger domain, is significantly reduced, while CK2α binding appears not affected. Other variants, p.Asp32Asn and p.Arg86Cys, did not affect stability or CK2β/α binding. For these mutants, the key to understanding the pathological mechanism may depend on external factors, such as altered protein-protein interaction. We conclude that Zinc-finger domain variants appear to destabilize the protein and affect holoenzyme formation, effectively reducing the pool of competent holoCK2. In the context of POBINDS, our findings suggest that Zinc-finger domain variants are likely to affect cells similarly to truncating and splicing variants with reduced translation of full-length CK2β.</p>","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":"139-154"},"PeriodicalIF":2.4,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143960535","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}