Biological Chemistry最新文献_第2页

The proteostasis burden of aneuploidy. 非整倍体的蛋白质抑制负担。

IF 2.9 4区生物学

Biological Chemistry Pub Date : 2025-04-14 DOI: 10.1515/hsz-2024-0163

Prince Saforo Amponsah, Zuzana Storchová

引用次数: 0

A CK2α' mutant indicating why CK2α and CK2α', the isoforms of the catalytic subunit of human protein kinase CK2, deviate in affinity to CK2β. 人类蛋白激酶CK2催化亚基的同工型CK2α和CK2α′对CK2β的亲和力偏离的原因是CK2α突变体。

IF 2.9 4区生物学

Biological Chemistry Pub Date : 2025-04-14 DOI: 10.1515/hsz-2024-0157

Christian Werner, Sophia Eimermacher, Hugo Harasimowicz, Dietmar Fischer, Markus Pietsch, Karsten Niefind

{"title":"A CK2α' mutant indicating why CK2α and CK2α', the isoforms of the catalytic subunit of human protein kinase CK2, deviate in affinity to CK2β.","authors":"Christian Werner, Sophia Eimermacher, Hugo Harasimowicz, Dietmar Fischer, Markus Pietsch, Karsten Niefind","doi":"10.1515/hsz-2024-0157","DOIUrl":"https://doi.org/10.1515/hsz-2024-0157","url":null,"abstract":"Protein kinase CK2 (casein kinase 2) mainly exists as heterotetrameric holoenzyme with two catalytic subunits (CK2α or CK2α') bound to a homodimer of non-catalytic subunits (CK2β). With CSNK2A1 and CSNK2A2, the human genome contains two paralogs encoding catalytic CK2 subunits. Both gene products, called CK2α and CK2α', strongly interact with CK2β. An earlier report that CK2α' has a lower CK2β affinity than CK2α is confirmed via isothermal titration calorimetry in this study. Furthermore, we show with a fluorescence-anisotropy assay that a CK2β-competitive peptide binds less strongly to CK2α' than to CK2α. The reason for the reduced affinity of CK2α' to CK2β and CK2β competitors is puzzling: both isoenzymes have identical amino acid compositions at their CK2β interfaces, but the β4β5 loop, a component of this interface, is conformationally less adaptable in CK2α' than in CK2α due to intramolecular constraints. To release these constraints, we constructed a CK2α' mutant that was equalized to CK2α at the backside of the β4β5 loop. Concerning thermostability, affinity to CK2β or CK2β competitors and 3D-structure next to the β4β5 loop, this CK2α' mutant is more similar to CK2α than to its own wild-type, suggesting a critical role of the β4β5 loop adaptability for CK2β affinity.","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143952940","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 nascent polypeptide-associated complex (NAC) as regulatory hub on ribosomes. 新生多肽相关复合体（NAC）作为核糖体的调控中心。

IF 2.9 4区生物学

Biological Chemistry Pub Date : 2025-04-02 DOI: 10.1515/hsz-2025-0114

Laurenz Rabl, Elke Deuerling

引用次数: 0

Unclogging of the TOM complex under import stress. 在进口压力下疏通TOM复合体。

IF 2.9 4区生物学

Biological Chemistry Pub Date : 2025-03-28 DOI: 10.1515/hsz-2025-0110

Joshua Jackson, Thomas Becker

{"title":"Unclogging of the TOM complex under import stress.","authors":"Joshua Jackson, Thomas Becker","doi":"10.1515/hsz-2025-0110","DOIUrl":"https://doi.org/10.1515/hsz-2025-0110","url":null,"abstract":"Mitochondrial functions and biogenesis depend on the import of more than 1,000 proteins which are synthesized as precursor proteins on cytosolic ribosomes. Mitochondrial protein translocases sort the precursor proteins into the mitochondrial sub-compartments: outer and inner membrane, the intermembrane space and the matrix. The translocase of the outer mitochondrial membrane (TOM complex) constitutes the major import site for most of these precursor proteins. Defective protein translocases, premature folding of the precursor, or depletion of the membrane potential can cause clogging of the TOM channel by a precursor protein. This clogging impairs further protein import and leads to accumulation of precursor proteins in the cell that perturbates protein homeostasis, leading to proteotoxic stress in the cell. Therefore, unclogging of the translocon is critical for maintaining mitochondrial and cellular function. Ubiquitylation and AAA-ATPases play a central role in the extraction of the precursor proteins to deliver them to the proteasome for degradation. Here we summarize our understanding of the molecular mechanisms that remove such translocation-stalled precursor proteins from the translocation channel to regenerate the TOM complex for protein import.","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727981","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

GPI-anchored serine proteases: essential roles in development, homeostasis, and disease. gpi锚定丝氨酸蛋白酶：在发育、体内平衡和疾病中的重要作用。

IF 2.9 4区生物学

Biological Chemistry Pub Date : 2025-03-17 Print Date: 2025-01-29 DOI: 10.1515/hsz-2024-0135

Joseph G Lundgren, Michael G Flynn, Karin List

引用次数: 0

Unfolded protein responses in Chlamydomonas reinhardtii. 莱茵衣藻对未折叠蛋白的响应。

IF 2.9 4区生物学

Biological Chemistry Pub Date : 2025-03-13 DOI: 10.1515/hsz-2025-0101

Sarah Gabelmann, Michael Schroda

{"title":"Unfolded protein responses in Chlamydomonas reinhardtii.","authors":"Sarah Gabelmann, Michael Schroda","doi":"10.1515/hsz-2025-0101","DOIUrl":"https://doi.org/10.1515/hsz-2025-0101","url":null,"abstract":"The disruption of protein homeostasis leads to the increased un- and misfolding of proteins and the formation of toxic protein aggregates. Their accumulation triggers an unfolded protein response that is characterized by the transcriptional upregulation of molecular chaperones and proteases, and aims to restore proteome integrity, maintain cellular function, suppress the cause of perturbation, and prevent disease and death. In the green microalga Chlamydomonas reinhardtii, the study of this response to proteotoxic stress has provided insights into the function of chaperone and protease systems, which are, though simpler, closely related to those found in land plants. In addition, there has been considerable progress in understanding the triggers and regulation of compartment-specific unfolded protein responses. This review provides an overview on how the dysfunction of protein homeostasis is sensed in the different compartments of Chlamydomonas, and summarizes the current knowledge on the pathways that are triggered to restore equilibrium in the cell, while also highlighting similarities and differences to the unfolded protein responses of other model organisms.","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603840","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

How neurons cope with oxidative stress. 神经元如何应对氧化应激。

IF 2.9 4区生物学

Biological Chemistry Pub Date : 2025-02-25 DOI: 10.1515/hsz-2024-0146

Johannes Ebding, Fiorella Mazzone, Stefan Kins, Jan Pielage, Tanja Maritzen

{"title":"How neurons cope with oxidative stress.","authors":"Johannes Ebding, Fiorella Mazzone, Stefan Kins, Jan Pielage, Tanja Maritzen","doi":"10.1515/hsz-2024-0146","DOIUrl":"10.1515/hsz-2024-0146","url":null,"abstract":"Neurons are highly dependent on mitochondrial respiration for energy, rendering them vulnerable to oxidative stress. Reactive oxygen species (ROS), by-products of oxidative phosphorylation, can damage lipids, proteins, and DNA, potentially triggering cell death pathways. This review explores the neuronal vulnerability to ROS, highlighting metabolic adaptations and antioxidant systems that mitigate oxidative damage. Balancing metabolic needs and oxidative stress defenses is critical for neurons, as disruptions are implicated in neurodegenerative diseases. Neurons uniquely modulate metabolic pathways, favoring glycolysis over oxidative phosphorylation in cell bodies, to minimize harmful ROS production. Key antioxidants, including superoxide dismutases and glutathione peroxidases, play crucial roles in neuronal protection, as evident from genetic studies linking deficiencies to neurodegeneration. Notably, neurons have the ability to adapt to oxidative conditions in compartment-specific manners and also utilize ROS as a signaling molecule to promote adaptive synaptic plasticity. Future research should aim to elucidate differential ROS signaling and antioxidant responses across neuronal compartments for improved therapeutic strategies.","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482006","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

Broadened substrate specificity of bacterial dipeptidyl-peptidase 7 enables release of half of all dipeptide combinations from peptide N-termini. 细菌二肽基肽酶7扩大了底物特异性，使一半的二肽组合从肽n端释放出来。

IF 2.9 4区生物学

Biological Chemistry Pub Date : 2025-02-10 Print Date: 2025-01-29 DOI: 10.1515/hsz-2024-0156

Kana Shirakura, Takayuki K Nemoto, Yuko Ohara Nemoto, Haruka Nishimata, Momo Sawase, Yu Shimoyama, Manami Nakasato-Suzuki, Kiyoshi Ito, Naomi Tanoue

{"title":"Broadened substrate specificity of bacterial dipeptidyl-peptidase 7 enables release of half of all dipeptide combinations from peptide N-termini.","authors":"Kana Shirakura, Takayuki K Nemoto, Yuko Ohara Nemoto, Haruka Nishimata, Momo Sawase, Yu Shimoyama, Manami Nakasato-Suzuki, Kiyoshi Ito, Naomi Tanoue","doi":"10.1515/hsz-2024-0156","DOIUrl":"10.1515/hsz-2024-0156","url":null,"abstract":"Dipeptide production mediated by dipeptidyl-peptidase (DPP)4, DPP5, DPP7, and DPP11 plays a crucial role in growth of Porphyromonas gingivalis, a periodontopathic asaccharolytic bacterium. Given the particular P1-position specificity of DPPs, it has been speculated that DPP5 or DPP7 might be responsible for degrading refractory P1 amino acids, i.e., neutral (Thr, His, Gly, Ser, Gln) and hydrophilic (Asn) residues. The present results identified DPP7 as an entity that processes these residues, thus ensuring complete production of nutritional dipeptides in the bacterium. Activity enhancement by the P1' residue was observed in DPP7, as well as DPP4 and DPP5. Toward the refractory P1 residues, DPP7 uniquely hydrolyzed HX|LD-MCA (X = His, Gln, or Asn) and their hydrolysis was most significantly suppressed in dpp7 gene-disrupted cells. Additionally, hydrophobic P2 residue significantly enhanced DPP7 activity toward these substrates. The findings propose a comprehensive 20 P1 × 20 P2 amino acid matrix showing the coordination of four DPPs to achieve complete dipeptide production along with subsidiary peptidases. The present finding of a broad substrate specificity that DPP7 accounts for releasing 48 % (192/400) of N-terminal dipeptides could implicate its potential role in linking periodontopathic disease to related systemic disorders.","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":"51-64"},"PeriodicalIF":2.9,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363482","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

Protein kinase CK2 contributes to glucose homeostasis. 蛋白激酶CK2有助于葡萄糖稳态。

IF 2.9 4区生物学

Biological Chemistry Pub Date : 2025-02-07 DOI: 10.1515/hsz-2024-0158

Claudia Götz, Mathias Montenarh

{"title":"Protein kinase CK2 contributes to glucose homeostasis.","authors":"Claudia Götz, Mathias Montenarh","doi":"10.1515/hsz-2024-0158","DOIUrl":"10.1515/hsz-2024-0158","url":null,"abstract":"In the early days of CK2 research, it was already published that the affinity of CK2 for its substrate casein was affected by insulin. Subsequent to the discovery of inhibitors of CK2 kinase activity, it was shown that CK2 has an influence on hormones that regulate glucose homeostasis and on enzymes that influence glucose metabolism in pancreatic islet cells as well as in hormone-sensitive target cells. This regulation includes the influence on transcription factors and thereby, gene expression, as well as direct modulation of the catalytic activity. The used CK2 inhibitors, especially the older ones, show a broad range of specificity, selectivity and off-target effects. Recently applied methods to down-regulate the expression of individual CK2 subunits using siRNA or CRISPR/Cas9 technology have contributed to the improvement of specificity. It was shown that inhibition of CK2 kinase activity or knock-down or knock-out of CK2α leads to an elevated synthesis and secretion of insulin in pancreatic β-cells and a down-regulation of the synthesis and secretion of glucagon from pancreatic α-cells. In the present review CK2-dependent molecular mechanisms will be addressed which contribute to the maintenance of glucose homeostasis.","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254548","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

MitoStores: stress-induced aggregation of mitochondrial proteins. 线粒体：应激诱导的线粒体蛋白聚集。

IF 2.9 4区生物学

Biological Chemistry Pub Date : 2025-01-21 DOI: 10.1515/hsz-2024-0148

Pragya Kaushik, Johannes M Herrmann, Katja G Hansen

{"title":"MitoStores: stress-induced aggregation of mitochondrial proteins.","authors":"Pragya Kaushik, Johannes M Herrmann, Katja G Hansen","doi":"10.1515/hsz-2024-0148","DOIUrl":"10.1515/hsz-2024-0148","url":null,"abstract":"Most mitochondrial proteins are synthesized in the cytosol and post-translationally imported into mitochondria. If the rate of protein synthesis exceeds the capacity of the mitochondrial import machinery, precursor proteins can transiently accumulate in the cytosol. The cytosolic accumulation of mitochondrial precursors jeopardizes cellular protein homeostasis (proteostasis) and can be the cause of diseases. In order to prevent these toxic effects, most non-imported precursors are rapidly degraded by the ubiquitin-proteasome system. However, cells employ a second layer of defense which is the facilitated sequestration of mitochondrial precursor proteins in transient protein aggregates. The formation of such structures is triggered by nucleation factors such as small heat shock proteins. Disaggregases and chaperones can liberate precursors from cytosolic aggregates to pass them on to the mitochondrial import machinery or, under persistent stress conditions, to the proteasome for degradation. Owing to their role as transient buffering systems, these aggregates were referred to as MitoStores. This review articles provides a general overview about the MitoStore concept and the early stages in mitochondrial protein biogenesis in yeast and, in cases where aspects differ, in mammalian cells.","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142999503","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