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Molecular insights into the modulation of the 5HT2A receptor by serotonin, psilocin, and the G protein subunit Gqα 5 -羟色胺、psilocin和G蛋白亚基Gqα对5HT2A受体调节的分子见解。
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2025-01-26 DOI: 10.1002/1873-3468.15099
Niklas Viohl, Ali Asghar Hakami Zanjani, Himanshu Khandelia
{"title":"Molecular insights into the modulation of the 5HT2A receptor by serotonin, psilocin, and the G protein subunit Gqα","authors":"Niklas Viohl,&nbsp;Ali Asghar Hakami Zanjani,&nbsp;Himanshu Khandelia","doi":"10.1002/1873-3468.15099","DOIUrl":"10.1002/1873-3468.15099","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <p>5HT<sub>2A</sub>R is a G-protein-coupled receptor that drives many neuronal functions and is a target for psychedelic drugs. Understanding ligand interactions and conformational transitions is essential for developing effective pharmaceuticals, but mechanistic details of 5HT<sub>2A</sub>R activation remain poorly understood. We utilized all-atom molecular dynamics simulations and free-energy calculations to investigate 5HT<sub>2A</sub>R's conformational dynamics upon binding to serotonin and psilocin. We show that the active state of 5HT<sub>2A</sub>R collapses to a closed state in the absence of Gqα, underscoring the importance of G-protein coupling. We discover an intermediate “partially-open” receptor conformation. Both ligands have higher binding affinities for the orthosteric than the extended binding pocket. These findings enhance our understanding of 5HT<sub>2A</sub>R's activation and may aid in developing novel therapeutics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <div>\u0000 <div>\u0000 \u0000 <h3>Impact statement</h3>\u0000 <p>This study sheds light on 5HT<sub>2A</sub>R activation, revealing intermediate conformations and ligand dynamics. These insights could enhance drug development for neurological and psychiatric disorders, benefiting researchers and clinicians in pharmacology and neuroscience.</p>\u0000 </div>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"599 6","pages":"876-891"},"PeriodicalIF":3.5,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/1873-3468.15099","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Interaction between bacterial phytochromes Agp1 and Agp2 of Agrobacterium fabrum by fluorescence resonance energy transfer and docking studies 法农杆菌光光色素Agp1和Agp2相互作用的荧光共振能量转移与对接研究
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2025-01-26 DOI: 10.1002/1873-3468.15102
Afaf El Kurdi, Gero Kaeser, Patrick Scheerer, David Hoffmann, Ebru Akkus, Marcus Elstner, Norbert Krauß, Tilman Lamparter
{"title":"Interaction between bacterial phytochromes Agp1 and Agp2 of Agrobacterium fabrum by fluorescence resonance energy transfer and docking studies","authors":"Afaf El Kurdi,&nbsp;Gero Kaeser,&nbsp;Patrick Scheerer,&nbsp;David Hoffmann,&nbsp;Ebru Akkus,&nbsp;Marcus Elstner,&nbsp;Norbert Krauß,&nbsp;Tilman Lamparter","doi":"10.1002/1873-3468.15102","DOIUrl":"10.1002/1873-3468.15102","url":null,"abstract":"<p>Phytochromes are biliprotein photoreceptors found in bacteria, fungi, and plants. The soil bacterium <i>Agrobacterium fabrum</i> has two phytochromes, Agp1 and Agp2, which work together to control DNA transfer to plants and bacterial conjugation. Both phytochromes interact as homodimeric proteins. For fluorescence resonance energy transfer (FRET) measurements, various Agp1 mutants and wild-type Agp2 were labeled with specific fluorophores to study their interaction. FRET efficiencies rose from position 122 to 545 of Agp1. The photosensory chromophore module (PCM) of Agp1 did not show a FRET signal, but the PCM of Agp2 did. Docking models suggest that Agp1 and Agp2 interact with their histidine kinase and PCM perpendicular to each, around 45 amino acids of Agp1 or Agp2 are involved.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"599 6","pages":"848-865"},"PeriodicalIF":3.5,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/1873-3468.15102","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Elucidation of interface interactions between a dehydratase domain and an acyl carrier protein in cremimycin polyketide synthase 阐明 Cremimycin 多酮合成酶中脱水酶结构域与酰基载体蛋白之间的界面相互作用。
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2025-01-26 DOI: 10.1002/1873-3468.15103
Kaede Kotagiri, Haruka Tachibana, Daisuke Kawasaki, Taichi Chisuga, Toma Kashima, Shinya Fushinobu, Fumitaka Kudo, Tadashi Eguchi, Akimasa Miyanaga
{"title":"Elucidation of interface interactions between a dehydratase domain and an acyl carrier protein in cremimycin polyketide synthase","authors":"Kaede Kotagiri,&nbsp;Haruka Tachibana,&nbsp;Daisuke Kawasaki,&nbsp;Taichi Chisuga,&nbsp;Toma Kashima,&nbsp;Shinya Fushinobu,&nbsp;Fumitaka Kudo,&nbsp;Tadashi Eguchi,&nbsp;Akimasa Miyanaga","doi":"10.1002/1873-3468.15103","DOIUrl":"10.1002/1873-3468.15103","url":null,"abstract":"<p>Modular polyketide synthases (PKSs) are multi-domain enzymes involved in the biosynthesis of polyketide natural products. The dehydratase (DH) domain catalyzes the dehydration of the β-hydroxyacyl unit attached to the acyl carrier protein (ACP) domain in modular PKS. Although the DH domain likely recognizes the cognate ACP domain during the dehydration reaction, the molecular basis of DH–ACP interactions remains elusive. In this study, we conducted cross-linking analysis using a pantetheine-type probe for investigating the ACP recognition of a fusion-DH protein generated from a split-DH domain of cremimycin PKS. Based on the AlphaFold 3-predicted model structure of the fusion-DH–ACP complex, DH–ACP interface residues were identified and validated by mutational analysis. Our findings provide the first detailed insights into domain–domain interactions between DH and ACP in modular PKSs.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"599 8","pages":"1159-1168"},"PeriodicalIF":3.5,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/1873-3468.15103","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Endothelial lipase-binding peptides similar to netrin-1 inhibit hepatitis B virus infection 类似netrin-1的内皮脂酶结合肽抑制乙型肝炎病毒感染。
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2025-01-25 DOI: 10.1002/1873-3468.15101
Mayuko Ide, Noriko Tabata, Kazuhisa Murai, Yuko Yonemura, Ying Wang, Atsuya Ishida, Takayoshi Shirasaki, Shuichi Kaneko, Satoru Ito, Masao Honda, Hiroshi Yanagawa
{"title":"Endothelial lipase-binding peptides similar to netrin-1 inhibit hepatitis B virus infection","authors":"Mayuko Ide,&nbsp;Noriko Tabata,&nbsp;Kazuhisa Murai,&nbsp;Yuko Yonemura,&nbsp;Ying Wang,&nbsp;Atsuya Ishida,&nbsp;Takayoshi Shirasaki,&nbsp;Shuichi Kaneko,&nbsp;Satoru Ito,&nbsp;Masao Honda,&nbsp;Hiroshi Yanagawa","doi":"10.1002/1873-3468.15101","DOIUrl":"10.1002/1873-3468.15101","url":null,"abstract":"<p>Hepatitis B virus (HBV) infects cells by attaching to heparan sulfate proteoglycans (HSPG) and Na<sup>+</sup>/taurocholate cotransporting polypeptide (NTCP). The endothelial lipase LIPG bridges HSPG and HBV, facilitating HBV attachment. From a randomized peptide expression library, we identified a short sequence binding to LIPG. This identified sequence closely resembled a sequence in the V domain of netrin-1, a protein known to bind heparin through its V domain. We designed two synthetic peptides based on this sequence and found that both synthetic peptides and netrin-1 suppressed HBV infection in chimeric mice with humanized livers and in primary hepatocytes isolated from them. The data reveal an antiviral function of the peptides and netrin-1 in HBV infection that is independent of LIPG lipase activity.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"599 9","pages":"1285-1298"},"PeriodicalIF":3.5,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045526","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
A histidine-rich extension of the mitochondrial F0 subunit ATP6 from the ice worm Mesenchytraeus solifugus increases ATP synthase activity in bacteria 冰虫Mesenchytraeus solifugus线粒体F0亚基ATP6的组氨酸丰富延伸增加了细菌中ATP合成酶的活性。
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2025-01-17 DOI: 10.1002/1873-3468.15100
Truman Dunkley, Daniel H. Shain, Eric A. Klein
{"title":"A histidine-rich extension of the mitochondrial F0 subunit ATP6 from the ice worm Mesenchytraeus solifugus increases ATP synthase activity in bacteria","authors":"Truman Dunkley,&nbsp;Daniel H. Shain,&nbsp;Eric A. Klein","doi":"10.1002/1873-3468.15100","DOIUrl":"10.1002/1873-3468.15100","url":null,"abstract":"<p>Bioenergetic profiles of psychrophiles across domains of life are unusual in that intracellular ATP levels increase with declining temperature. Whole-transcriptome sequencing of the glacier ice worm <i>Mesenchytraeus solifugus</i> revealed a unique C-terminal extension on the ATP6 protein, which forms part of the proton pore of mitochondrial ATP synthase (Complex V). This extension, positioned near the proton exit pore, comprises alternating histidine residues thought to increase proton flux through Complex V leading to elevated ATP synthesis. To test this hypothesis, we fused the <i>M. solifugus</i> C-terminal extension to <i>Escherichia coli</i> AtpB (the ATP6 orthologue) and observed a ~ 5-fold increase in ATP synthesis. This enhancement was unidirectional as we observed no change to ATP hydrolysis rates. These findings offer an avenue for identifying critical factors associated with ice worm adaptation.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"599 8","pages":"1113-1121"},"PeriodicalIF":3.5,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/1873-3468.15100","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Diphthamide synthesis is linked to the eEF2-client chaperone machinery 双苯二胺的合成与eef2 -客户伴侣机制有关。
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2025-01-17 DOI: 10.1002/1873-3468.15095
Lars Kaduhr, Klaus Mayer, Raffael Schaffrath, Johannes Buchner, Ulrich Brinkmann
{"title":"Diphthamide synthesis is linked to the eEF2-client chaperone machinery","authors":"Lars Kaduhr,&nbsp;Klaus Mayer,&nbsp;Raffael Schaffrath,&nbsp;Johannes Buchner,&nbsp;Ulrich Brinkmann","doi":"10.1002/1873-3468.15095","DOIUrl":"10.1002/1873-3468.15095","url":null,"abstract":"<p>The diphthamide modification of eukaryotic translation elongation factor (eEF2) is important for accurate protein synthesis. While the enzymes for diphthamide synthesis are known, coordination of eEF2 synthesis with the diphthamide modification to maintain only modified eEF2 is unknown. Physical and genetic interactions extracted from BioGRID show a connection between diphthamide synthesis enzymes and chaperones in yeast. This includes the Hsp90 co-chaperones Hgh1 and Cpr7. The respective co-chaperone deletion strains contained eEF2 without diphthamide. Notably, strains deficient in other co-chaperones showed no defect in the eEF2-diphthamide modification. Our results demonstrate that diphthamide synthesis involves not only Dph enzymes but also the eEF2-interacting co-chaperones Hgh1 and Cpr7 and may thus require a conformational state of eEF2 which is maintained by specific (co-)chaperones.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"599 9","pages":"1260-1268"},"PeriodicalIF":3.5,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/1873-3468.15095","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Characterization of fungal carbonyl sulfide hydrolase belonging to clade D β-carbonic anhydrase 真菌羰基硫化物水解酶D支β-碳酸酐酶的鉴定。
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2025-01-10 DOI: 10.1002/1873-3468.15098
Ryuka Iizuka, Takahiro Ogawa, Rikako Tsukida, Keiichi Noguchi, David Hibbett, Yoko Katayama, Makoto Yoshida
{"title":"Characterization of fungal carbonyl sulfide hydrolase belonging to clade D β-carbonic anhydrase","authors":"Ryuka Iizuka,&nbsp;Takahiro Ogawa,&nbsp;Rikako Tsukida,&nbsp;Keiichi Noguchi,&nbsp;David Hibbett,&nbsp;Yoko Katayama,&nbsp;Makoto Yoshida","doi":"10.1002/1873-3468.15098","DOIUrl":"10.1002/1873-3468.15098","url":null,"abstract":"<p>Carbonyl sulfide hydrolase (COSase) is a unique enzyme that exhibits high activity towards carbonyl sulfide (COS) but low carbonic anhydrase (CA) activity, despite belonging to the CA family. COSase was initially identified in a sulfur-oxidizing bacterium and later discovered in the ascomycete <i>Trichoderma harzianum</i> strain THIF08. The COSase from <i>T. harzianum</i> has been recognized as a key enzyme in the assimilation of gaseous COS, and homologous genes are widely present not only in Ascomycota but also in Basidiomycota. Here, we characterized the COSases from the basidiomycete <i>Gloeophyllum trabeum</i> NBRC 6430 and <i>T. harzianum</i> to obtain detailed characteristics of fungal COSase. This study contributes to a better understanding of COS metabolism in fungi.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"599 8","pages":"1146-1158"},"PeriodicalIF":3.5,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/1873-3468.15098","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142962146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Calcium-sensing receptor- and ADAM10-mediated klotho shedding is regulated by tetraspanin 5 钙敏感受体和adam10介导的klotho脱落是由tetraspanin5调节的。
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2025-01-07 DOI: 10.1002/1873-3468.15078
Zhenan Liu, Joonho Yoon, Eunyoung Lee, Audrey N. Chang, R. Tyler Miller
{"title":"Calcium-sensing receptor- and ADAM10-mediated klotho shedding is regulated by tetraspanin 5","authors":"Zhenan Liu,&nbsp;Joonho Yoon,&nbsp;Eunyoung Lee,&nbsp;Audrey N. Chang,&nbsp;R. Tyler Miller","doi":"10.1002/1873-3468.15078","DOIUrl":"10.1002/1873-3468.15078","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <p>Soluble, circulating Klotho (sKlotho) is essential for normal health and renal function. sKlotho is shed from the renal distal convoluted tubule (DCT), its primary source, via enzymatic cleavage. However, the physiologic mechanisms that control sKlotho production, trafficking, and shedding are not fully defined. We previously found that the G protein-coupled calcium-sensing receptor (CaSR) co-localizes with membrane-bound αKlotho and the disintegrin/metalloprotease ADAM10 in the DCT and controls sKlotho in response to CaSR ligands and pHo by activating ADAM10. Here, we advance understanding of this process by showing that tetraspanin 5 (Tspan5), a scaffolding and chaperone protein, contributes to the cell surface expression and specificity of a protein complex that includes Tspan5, ADAM10, Klotho, and CaSR. These results support a model of multiprotein complexes that confer signaling specificity beyond CaSR on G protein-coupled processes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <div>\u0000 <div>\u0000 \u0000 <h3>Impact statement</h3>\u0000 <p>Systemic circulating sKlotho is a determinant for normal physiology. Studies of knockout animals established its role as an anti-aging protein. The regulatory mechanisms for Klotho production and secretion are largely unknown. We report that Tspan 5 contributes to CaSR- and ADAM10-dependent Klotho shedding from the kidney, its primary source.</p>\u0000 </div>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"599 6","pages":"866-875"},"PeriodicalIF":3.5,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/1873-3468.15078","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Ligand recognition by 14-3-3 proteins requires negative charges but not necessarily phosphorylation 14-3-3蛋白对配体的识别需要负电荷，但不一定需要磷酸化。
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2025-01-05 DOI: 10.1002/1873-3468.15077
Seraphine Kamayirese, Laura A. Hansen, Sándor Lovas
{"title":"Ligand recognition by 14-3-3 proteins requires negative charges but not necessarily phosphorylation","authors":"Seraphine Kamayirese,&nbsp;Laura A. Hansen,&nbsp;Sándor Lovas","doi":"10.1002/1873-3468.15077","DOIUrl":"10.1002/1873-3468.15077","url":null,"abstract":"<p>Protein–protein interactions involving 14-3-3 proteins regulate various cellular activities in normal and pathological conditions. These interactions have mostly been reported to be phosphorylation-dependent, but the 14-3-3 proteins also interact with unphosphorylated proteins. In this work, we investigated whether phosphorylation is required, or, alternatively, whether negative charges are sufficient for 14-3-3ε binding. We substituted the pThr residue of pT(502–510) peptide by residues with a varying number of negative charges and investigated the binding of the peptides to 14-3-3ε using MD simulations and biophysical methods. We demonstrated that at least one negative charge is required for the peptides to bind 14-3-3ε, although phosphorylation is not necessary, and that two negative charges are preferable for high affinity binding. This discovery opens up new approaches for designing peptide-based 14-3-3 protein inhibitors.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"599 6","pages":"838-847"},"PeriodicalIF":3.5,"publicationDate":"2025-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/1873-3468.15077","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142931102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The [2Fe-2S] cluster of mitochondrial outer membrane protein mitoNEET has an O2-regulated nitric oxide access tunnel 线粒体外膜蛋白mitoNEET的[2Fe-2S]簇具有o2调节的一氧化氮通道。
IF 3.5 4区 生物学
FEBS Letters Pub Date : 2025-01-05 DOI: 10.1002/1873-3468.15097
Thao Nghi Hoang, Meritxell Wu-Lu, Alberto Collauto, Peter-Leon Hagedoorn, Madalina Alexandru, Maike Henschel, Shahram Kordasti, Maria Andrea Mroginski, Maxie M. Roessler, Kourosh H. Ebrahimi
{"title":"The [2Fe-2S] cluster of mitochondrial outer membrane protein mitoNEET has an O2-regulated nitric oxide access tunnel","authors":"Thao Nghi Hoang,&nbsp;Meritxell Wu-Lu,&nbsp;Alberto Collauto,&nbsp;Peter-Leon Hagedoorn,&nbsp;Madalina Alexandru,&nbsp;Maike Henschel,&nbsp;Shahram Kordasti,&nbsp;Maria Andrea Mroginski,&nbsp;Maxie M. Roessler,&nbsp;Kourosh H. Ebrahimi","doi":"10.1002/1873-3468.15097","DOIUrl":"10.1002/1873-3468.15097","url":null,"abstract":"<p>The mitochondrial outer membrane iron–sulphur ([Fe-S]) protein mitoNEET has been extensively studied as a target of the anti-inflammatory and type-2 diabetes drug pioglitazone and as a protein affecting mitochondrial respiratory rate. Despite these extensive past studies, its molecular function has yet to be discovered. Here, we applied an interdisciplinary approach and discovered an explicit nitric oxide (NO) access site to the mitoNEET [2Fe-2S] cluster. We found that O<sub>2</sub> and pioglitazone block NO access to the cluster, suggesting a molecular function for the mitoNEET [2Fe-2S] cluster in mitochondrial signal transduction. Our discovery hints at a new pathway <i>via</i> which mitochondria can sense hypoxia through O<sub>2</sub> protection of the mitoNEET [2Fe-2S] cluster, a new paradigm in understanding the importance of [Fe-S] clusters for gasotransmitter signal transduction in eukaryotes.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":"599 7","pages":"952-970"},"PeriodicalIF":3.5,"publicationDate":"2025-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/1873-3468.15097","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142931103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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