Biochemical Journal最新文献

Vesicular transport in the autophagic route: RAB GTPases as pivotal regulators of autophagy. 自噬途径中的囊泡运输：RAB gtpase作为自噬的关键调节因子。

IF 4.1 3区生物学

Biochemical Journal Pub Date : 2025-10-17 DOI: 10.1042/bcj20253092

Romina Abba,María Isabel Colombo

引用次数: 0

Kinetic investigation of calcium-induced Sorcin aggregation by stopped-flow light scattering. 用停止流光散射研究钙诱导Sorcin聚集的动力学。

IF 4.3 3区生物学

Biochemical Journal Pub Date : 2025-10-15 DOI: 10.1042/BCJ20253194

Qiushi Ye, Kathleen Joyce Carillo, Nicolas Delaeter, Lei Zhang, Jaekyun Jeon, Yanxin Liu

{"title":"Kinetic investigation of calcium-induced Sorcin aggregation by stopped-flow light scattering.","authors":"Qiushi Ye, Kathleen Joyce Carillo, Nicolas Delaeter, Lei Zhang, Jaekyun Jeon, Yanxin Liu","doi":"10.1042/BCJ20253194","DOIUrl":"https://doi.org/10.1042/BCJ20253194","url":null,"abstract":"Sorcin, a penta-EF hand calcium-binding protein, is implicated in multidrug resistance (MDR) in various cancers and has roles in neurodegenerative diseases. It regulates cellular calcium homeostasis by interacting with calcium channels, pumps, and exchangers in a calcium-dependent manner. Calcium binding induces a conformational change in Sorcin, exposing hydrophobic surfaces that mediate protein interactions and calcium flux between the cytosol and endoplasmic reticulum (ER). These exposed surfaces can also drive Sorcin aggregation in the absence of binding partners. Here, we exploited calcium-induced conformational changes and aggregation of Sorcin as a model to study its calcium sensitivity and aggregation mechanisms. Stopped-flow light scattering revealed that Sorcin aggregation is reversible, cooperative, and primarily influenced by Sorcin concentration rather than physiological calcium levels. Our findings suggest that calcium sensitivity of Sorcin is finely tuned by its expression level, highlighting its role as an intracellular calcium sensor. This work establishes Sorcin as a model system for studying protein aggregation mechanisms with implications for MDR and neurodegenerative diseases.","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145353536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

AmyloGram Reveals Amyloidogenic Potential in Stroke Thrombus Proteomes. 淀粉图揭示中风血栓蛋白质组中淀粉样变性的潜力。

IF 4.3 3区生物学

Biochemical Journal Pub Date : 2025-10-10 DOI: 10.1042/BCJ20253317

Douglas B Kell, Karen M Doyle, J Salcedo-Sora, Alakendu Sekhar, Melanie Walker, Etheresia Pretorius

{"title":"AmyloGram Reveals Amyloidogenic Potential in Stroke Thrombus Proteomes.","authors":"Douglas B Kell, Karen M Doyle, J Salcedo-Sora, Alakendu Sekhar, Melanie Walker, Etheresia Pretorius","doi":"10.1042/BCJ20253317","DOIUrl":"https://doi.org/10.1042/BCJ20253317","url":null,"abstract":"Amyloidogenic proteins play a central role in a range of pathological conditions, yet their presence in thrombi has only recently been recognized. Whether computational prediction tools can identify amyloid-forming potential in thrombus proteomes remains unclear. AmyloGram is a computational tool that estimates amyloid-forming potential based on n-gram sequence encoding and random forest classification. Using AmyloGram, we analyzed 204 proteins in UniProt that were tagged by humans as amyloidogenic. We then applied the same approach to proteins identified in thrombi retrieved using mechanical thrombectomy from patients with cardioembolic and atherothrombotic stroke. In addition we used AmyloGram to analyse the amyloidogenicity of 83,567 canonical human protein sequences. Among the UniProt-annotated 'amyloid' set, nearly all proteins received AmyloGram scores above 0.7, including 23 of the 24 human proteins. Even the lowest-scoring human protein, lysozyme (scoring 0.675), is known to form amyloid under certain conditions. In thrombi from both stroke subtypes in four different studies, all detected proteins (with a single exception) had AmyloGram scores above 0.7, suggesting a high likelihood of amyloid content. A majority of unannotated proteins also achieve AmyloGram scores exceeding 0.7. AmyloGram reliably identifies known amyloid-forming proteins and reveals that stroke thrombi are enriched for proteins with high amyloidogenic potential. These findings support the hypothesis that thrombus formation in stroke involves amyloid-related mechanisms and warrant further investigation using histological and functional validation.","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145298131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Extracellular Vesicle-Linked Vitamin B12 Acquisition via Novel Binding Proteins in Bacteroides thetaiotaomicron. 在拟杆菌中通过新的结合蛋白获得细胞外囊泡连接的维生素B12。

IF 4.1 3区生物学

Biochemical Journal Pub Date : 2025-10-10 DOI: 10.1042/bcj20253340

Rokas Juodeikis,Robert Ulrich,Charlea Clarke,Michal Banasik,Evelyne Deery,Gerhard Saalbach,Bernhard Kräutler,Simon R Carding,Michael A Geeves,Richard Pickersgill,Martin J Warren

{"title":"Extracellular Vesicle-Linked Vitamin B12 Acquisition via Novel Binding Proteins in Bacteroides thetaiotaomicron.","authors":"Rokas Juodeikis,Robert Ulrich,Charlea Clarke,Michal Banasik,Evelyne Deery,Gerhard Saalbach,Bernhard Kräutler,Simon R Carding,Michael A Geeves,Richard Pickersgill,Martin J Warren","doi":"10.1042/bcj20253340","DOIUrl":"https://doi.org/10.1042/bcj20253340","url":null,"abstract":"Vitamin B12 (cobalamin) and related cobamides are essential cofactors for many gut bacteria, yet their acquisition requires complex uptake systems due to limited availability. In the human gut commensal Bacteroides thetaiotaomicron, cobamide uptake is mediated by multiple operons encoding outer membrane proteins, transporters and uncharacterised lipoproteins, some of which are incorporated into bacterial extracellular vesicles (BEVs). Here, we advance the functional and structural understanding of this cobamide acquisition system by examining previously uncharacterized features. Bioinformatic and promoter-reporter analyses revealed four uptake operons, including novel genes we designate btuK, btuJ, btuL and btuX, with evidence for internal promoters and riboswitch regulation. Recombinant expression and binding assays identified ten cobamide-binding proteins, including three novel lipoproteins (BtuK1, BtuJ1 and BtuJ2). Biophysical measurements demonstrated affinities in the nano- to picomolar range, with BtuJ proteins displaying exceptionally tight binding. High-resolution crystal structures of BtuJ1 and BtuJ2 revealed an augmented β-jelly-roll fold, with conserved tyrosine residues forming a \"halo\" around the corrin, suggesting a conserved binding mechanism within the IPR027828 protein family. Comparative proteomics of cells and BEVs under cobamide starvation showed selective enrichment of BtuJ and BtuL in BEVs. Functional assays demonstrated that BEV-mediated cobamide uptake depends specifically on BtuJ1 and BtuJ2, whereas BtuL promotes early-phase BEV release. These findings establish the BtuJ proteins as critical BEV-associated cobamide-binding components, provide structural insights into their tight binding, and suggest a model where BEVs act analogously to siderophores, capturing cobamides for delivery to cells. This work highlights the central role of BEVs in microbial nutrient competition.","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":"1 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145288476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Lon/Pim1 mediated degradation of presequence translocase-associated motor components Pam16 and Pam18 in Saccharomyces cerevisiae. 在酿酒酵母中，Lon/Pim1介导的前序转位酶相关运动成分Pam16和Pam18的降解。

IF 4.1 3区生物学

Biochemical Journal Pub Date : 2025-10-10 DOI: 10.1042/bcj20243016

Yerranna Boggula,Arpan Chatterjee,Gaurav Simaiya,Amita Pal,Akash Srinivasan,Naresh Babu Sepuri

引用次数: 0

Penetrant PKCb mutation in ATLL displays a mixed gain-of-function. ATLL的显性PKCb突变表现为混合功能增益。

IF 4.1 3区生物学

Biochemical Journal Pub Date : 2025-10-10 DOI: 10.1042/bcj20253384

Sophie J L Brown,David C Briggs,Patrick Costello,Hiroko Yaguchi,Charles R M Bangham,Peter J Parker,Neil Q McDonald

引用次数: 0

Plasma membrane folate transport in fungi and plants is mediated by members of the oligopeptide transporter (OPT) family. 真菌和植物的质膜叶酸转运是由寡肽转运蛋白（OPT）家族成员介导的。

IF 4.3 3区生物学

Biochemical Journal Pub Date : 2025-10-10 DOI: 10.1042/BCJ20253359

Nikita Vashist, Md Shabbir Ahmad, Sahithi Vedula, Chinmayee Choudhury, Sunil Laxman, Anand K Bachhawat

{"title":"Plasma membrane folate transport in fungi and plants is mediated by members of the oligopeptide transporter (OPT) family.","authors":"Nikita Vashist, Md Shabbir Ahmad, Sahithi Vedula, Chinmayee Choudhury, Sunil Laxman, Anand K Bachhawat","doi":"10.1042/BCJ20253359","DOIUrl":"https://doi.org/10.1042/BCJ20253359","url":null,"abstract":"Folates are essential for all organisms. They are acquired either through de novo biosynthesis or from the diet. Yeast, fungi and plants make their own folates and it has not been clear if plasma membrane folate transporters exist in these organisms. Using a synthetic lethal screen in Saccharomyces cerevisiae we observed that deletions in a gene encoding the previously identified glutathione transporter, OPT1, exhibited severe growth defect with a disruption in folate biosynthesis. Uptake experiments confirmed that Opt1p/Hgt1p can transport folinic acid and the naturally abundant methyl tetrahydrofolate. As cerevisiae Opt1p was able to transport both folate and glutathione, we used alanine-scanning mutants of the residues in the transmembrane domains of the channel pore to identify the residues required specifically for the uptake of folates and distinct from those required for glutathione. We further examined the oligopeptide transporter family of other organisms for the presence of folate transporters. In C. albicans, CaOPT1, the orthologue of cerevisiae OPT1 efficiently transported folate but not glutathione, while the previously characterized glutathione transporter, CaOPT7 could not transport folate. Aspergillus fumigatus has eight homologues of the oligopeptide transporter family, of which OptB and OptH transport folates. In the plant Arabidopsis thaliana, the Opt1 homologs AtOpt2, AtOpt4, and AtOpt6 transport folates. This discovery of folate transporters across fungi and plants fills a critical gap in our understanding of folate metabolism, and can benefit the exploitation of these pathways in pathogenic fungi, and in plants.","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145290719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Cell membrane asymmetries and cellular aging. 细胞膜不对称与细胞老化。

IF 4.1 3区生物学

Biochemical Journal Pub Date : 2025-10-09 DOI: 10.1042/bcj20253265

Valentina Salzman,Pablo S Aguilar

引用次数: 0

Correction: Phosphoinositide 3-kinase-dependent phosphorylation of the dual adaptor for phosphotyrosine and 3-phosphoinositides by the Src family of tyrosine kinase. 更正：酪氨酸激酶Src家族对磷酸酪氨酸和3-磷酸肌苷双接头的磷酸化依赖。

IF 4.3 3区生物学

Biochemical Journal Pub Date : 2025-10-09 DOI: 10.1042/BCJ3490605_COR

引用次数: 0

Phosphorus-specific, liquid chromatography inductively coupled plasma mass-spectrometry for analysis of inositol phosphate and inositol pyrophosphate metabolism. 磷酸特异性液相色谱-电感耦合等离子体质谱法分析磷酸肌醇和焦磷酸肌醇代谢。

IF 4.1 3区生物学

Biochemical Journal Pub Date : 2025-10-02 DOI: 10.1042/bcj20253151

Colleen Sprigg,Hayley L Whitfield,Philip T Leftwich,Hui-Fen Kuo,Tzyy-Jen Chiou,Adolfo Saiardi,Megan L Shipton,Andrew M Riley,Barry V L Potter,Dawn Scholey,Emily Burton,Mike R Bedford,Charles A Brearley

{"title":"Phosphorus-specific, liquid chromatography inductively coupled plasma mass-spectrometry for analysis of inositol phosphate and inositol pyrophosphate metabolism.","authors":"Colleen Sprigg,Hayley L Whitfield,Philip T Leftwich,Hui-Fen Kuo,Tzyy-Jen Chiou,Adolfo Saiardi,Megan L Shipton,Andrew M Riley,Barry V L Potter,Dawn Scholey,Emily Burton,Mike R Bedford,Charles A Brearley","doi":"10.1042/bcj20253151","DOIUrl":"https://doi.org/10.1042/bcj20253151","url":null,"abstract":"Inositol phosphate (InsP) and diphosphoinositol phosphate (PP-InsP) analysis in tissues is plagued by multiple difficulties of sensitivity, regioisomer resolution and the need for radiolabeling with metabolic precursors. We describe a liquid chromatography (LC) inductively coupled plasma (ICP) mass spectrometry (MS) method (LC-ICP-MS) that addresses all such issues and use LC-ICP-MS to analyse InsPs in avian tissues. The highly sensitive technique tolerates complex matrices and, by powerful chromatography, resolves in a single run multiple non-enantiomeric myo-inositol tetrakisphosphates, myo-inositol pentakisphosphates and all inositol hexakisphosphates, including myo-inositol 1,2,3,4,5,6-hexakisphosphate (phytate), known in nature. It also separates and quantifies diphospho myo-inositol pentakisphosphate (PP-InsP5) isomers from their biological precursors and from 1,5-bis-diphospho myo-inositol 2,3,4,6 tetrakisphosphate (1,5-[PP]2-InsP4). Gut tissue inositol phosphates, belonging to a non-canonical, lipid-independent pathway, are shown to differ from phytate digestion products and to be responsive to diet.","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":"22 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145235869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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