FEBS Letters最新文献_第5页

Mutational analysis of Yih1 and IMPACT reveals amino acids required for Gcn2 inhibition. yyh1和IMPACT的突变分析揭示了抑制Gcn2所需的氨基酸。

IF 3 4区生物学

FEBS Letters Pub Date : 2025-08-27 DOI: 10.1002/1873-3468.70148

Bianca J M Sansom, Victoria J Gibbs, Anja H Schiemann, Evelyn Sattlegger

引用次数: 0

Thermostable neutral metalloprotease from Geobacillus sp. EA1 does not share thermolysin's preference for substrates with leucine at the P1' position. 来自Geobacillus sp. EA1的耐热中性金属蛋白酶不像热溶素那样偏爱在P1'位置有亮氨酸的底物。

IF 3 4区生物学

FEBS Letters Pub Date : 2025-08-25 DOI: 10.1002/1873-3468.70123

Grant R Broomfield, Torsten Kleffmann, David J Saul, Sigurd M Wilbanks

{"title":"Thermostable neutral metalloprotease from Geobacillus sp. EA1 does not share thermolysin's preference for substrates with leucine at the P1' position.","authors":"Grant R Broomfield, Torsten Kleffmann, David J Saul, Sigurd M Wilbanks","doi":"10.1002/1873-3468.70123","DOIUrl":"https://doi.org/10.1002/1873-3468.70123","url":null,"abstract":"Cleavage preference determines suitability of proteases for different applications. The cleavage preference of a thermophilic neutral metalloprotease (npr) from Geobacillus sp. EA1 was characterised using mass spectrometry, confirming its similarity to thermolysin in preferring P1' hydrophobic amino acids. While EA1 npr showed similar efficiencies while cleaving short peptides with any one of six hydrophobic amino acids at the P1' position, thermolysin showed marked preference for leucine. A single amino acid difference in the S1' pocket of these enzymes underlies this difference. A variant of EA1 npr (F133L) had intermediate preference, suggesting that approximately half the difference is attributable to this single amino acid change. Broader preference and higher efficiency make EA1 npr a superior candidate for quick digestion of varied substrates. Impact statement This investigation supported two new, useful conclusions. It characterised for the first time the substrate preference of EA1, a commercially significant protease. In the course of comparison to the very well-studied thermolysin, a hitherto unknown subtlety of thermolysin's substrate preference (marked preference for leucine) was found.","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144948044","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

Biochemical mechanism of the mammalian circadian clock. 哺乳动物生物钟的生化机制。

IF 3 4区生物学

FEBS Letters Pub Date : 2025-08-25 DOI: 10.1002/1873-3468.70150

Yang Liu, Aziz Sancar

{"title":"Biochemical mechanism of the mammalian circadian clock.","authors":"Yang Liu, Aziz Sancar","doi":"10.1002/1873-3468.70150","DOIUrl":"https://doi.org/10.1002/1873-3468.70150","url":null,"abstract":"Circadian rhythms, regulated by core clock proteins, coordinate physiological functions with daily environmental fluctuations across organisms, from bacteria to humans. The circadian clock interacts with various biological processes, and its disruption is associated with numerous human diseases, including sleep disorders, metabolic syndrome, and potentially cancer. In mammals, the circadian clock is driven by cell-autonomous transcription-translation feedback loops (TTFLs), in which CLOCK and BMAL1 act as transcriptional activators, while PER and CRY serve as transcriptional repressors. During the early repression phase, the CRY-PER-CK1 complex binds to CLOCK-BMAL1, displacing it from target promoters. In the late repression phase, in the absence of PER, CRY1 alone inhibits CLOCK-BMAL1 activity by blocking the recruitment of transcriptional coactivators. Biochemical and structural studies have highlighted the essential roles of protein-protein interactions, protein-DNA interactions, and posttranslational modifications in regulating the molecular clock. In this Review, we summarize the molecular mechanisms that govern the circadian clock and focus on the coordination of protein-protein interactions and posttranslational modifications, underscoring the importance of the circadian clock in disease progression and treatment strategies.","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12380416/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144948152","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

Spatial regulation of ARL3 and GSF-mediated lipidated cargo trafficking in the primary cilium. 初级纤毛中ARL3和gsf介导的脂质货物运输的空间调节。

IF 3 4区生物学

FEBS Letters Pub Date : 2025-08-21 DOI: 10.1002/1873-3468.70145

Hanne Peeters, Shehab Ismail

{"title":"Spatial regulation of ARL3 and GSF-mediated lipidated cargo trafficking in the primary cilium.","authors":"Hanne Peeters, Shehab Ismail","doi":"10.1002/1873-3468.70145","DOIUrl":"https://doi.org/10.1002/1873-3468.70145","url":null,"abstract":"Lipid-modified proteins are essential for ciliary signaling and structure, but their hydrophobic modifications hinder cytosolic transport and selective delivery. GDI-like solubilizing factors (GSFs), such as PDE6D and UNC119A/B, bind lipid moieties to shield cargo proteins and enable diffusion. However, the mechanisms that govern spatially restricted cargo release-particularly at the primary cilium-are not fully elucidated yet. In this Review, we highlight the central role of the small G protein ARL3 and its regulators in mediating selective release of lipidated cargoes. We discuss ARL13B, a ciliary-localized guanine nucleotide exchange factor (GEF) for ARL3, and BART, a co-GEF that enhances ARL3 activation by relieving autoinhibition. In contrast, RP2, a GTPase-activating protein (GAP) at the ciliary base, likely inactivates ARL3 outside the cilium, establishing a spatial ARL3·GTP gradient that restricts cargo release. Additional specificity arises from ARL2 exclusion from the cilium, differential GSF-cargo binding affinities, and putative docking platforms such as RPGR. Disruption of this pathway is implicated in ciliopathies, including Joubert syndrome. Current models and recent findings provide a framework for understanding spatial GTPase signaling in ciliary transport.","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144947938","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 nicotinamide hypothesis revisited-plant defense signaling integrating PARP, nicotinamide, nicotinic acid, epigenetics, and glutathione. 烟酰胺假说被重新审视——整合PARP、烟酰胺、烟酸、表观遗传学和谷胱甘肽的植物防御信号。

IF 3 4区生物学

FEBS Letters Pub Date : 2025-08-20 DOI: 10.1002/1873-3468.70146

Torkel Berglund, Anna B Ohlsson

引用次数: 0

Kit structural mutations associated with the porcine dominant white phenotype impair hematopoiesis in mice. 与猪显性白色表型相关的试剂盒结构突变损害小鼠造血功能。

IF 3 4区生物学

FEBS Letters Pub Date : 2025-08-19 DOI: 10.1002/1873-3468.70144

Chong Zhang, Zhiting Feng, Min Yang, Peiqing Cong, Xiaohong Liu, Yaosheng Chen, Zuyong He

引用次数: 0

EGTA-induced disruption of adherens junctions in zebrafish embryonic epidermis. egta诱导斑马鱼胚胎表皮粘附连接的破坏。

IF 3 4区生物学

FEBS Letters Pub Date : 2025-08-13 DOI: 10.1002/1873-3468.70142

M Florencia Sampedro, Marta E Sian, Paulo E Cabral Filho, Adriana Fontes, Valeria Sigot

引用次数: 0

The multidrug and toxin extrusion (MATE) transporter DTX51 antagonizes non-cell-autonomous HLS1-AMP1 signaling in a region-specific manner. 多药和毒素挤出（MATE）转运体DTX51以区域特异性方式拮抗非细胞自主的HLS1-AMP1信号。

IF 3 4区生物学

FEBS Letters Pub Date : 2025-08-13 DOI: 10.1002/1873-3468.70134

Takashi Nobusawa, Makoto Kusaba

{"title":"The multidrug and toxin extrusion (MATE) transporter DTX51 antagonizes non-cell-autonomous HLS1-AMP1 signaling in a region-specific manner.","authors":"Takashi Nobusawa, Makoto Kusaba","doi":"10.1002/1873-3468.70134","DOIUrl":"https://doi.org/10.1002/1873-3468.70134","url":null,"abstract":"Multidrug and toxin extrusion (MATE) transporters are widely conserved across all domains of life and play diverse roles in plant development. Here, we investigated the role of DETOXIFICATION 51 (DTX51), a MATE transporter in Arabidopsis. Overexpression of DTX51 led to pleiotropic phenotypes resembling those of hls1 hlh1 and amp1 lamp1 loss-of-function mutants, which have disruptions of key developmental regulators that act non-cell-autonomously. Genetic and gene expression analyses revealed that DTX51 and HLS1 act within the same genetic pathway, forming a negative feedback loop at the transcriptional level. Spatially restricted overexpression experiments showed that, in contrast to HLS1 and AMP1, DTX51 acts in a region-specific manner within the shoot apical meristem, suggesting that DTX51 fine-tunes development locally by modulating non-cell-autonomous signals. Impact statement This study reveals a role of the MATE transporter DTX51, whose transport substrate remains unknown, in Arabidopsis development, providing new insights into how this transporter fine-tunes non-cell-autonomous signals generated by the HLS1-AMP1 module.","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144947945","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

Structural diversity of pyruvate dehydrogenase complexes. 丙酮酸脱氢酶复合物的结构多样性。

IF 3 4区生物学

FEBS Letters Pub Date : 2025-08-13 DOI: 10.1002/1873-3468.70140

Sarah N Bothe, Rafal Zdanowicz

{"title":"Structural diversity of pyruvate dehydrogenase complexes.","authors":"Sarah N Bothe, Rafal Zdanowicz","doi":"10.1002/1873-3468.70140","DOIUrl":"https://doi.org/10.1002/1873-3468.70140","url":null,"abstract":"The pyruvate dehydrogenase complex (PDHc) is a crucial metabolic enzyme complex found in all aerobic organisms. It catalyzes the conversion of pyruvate, the product of glycolysis, into acetyl-CoA, a key substrate for the citric acid cycle and fatty acid synthesis. This multienzyme complex uses multiple cosubstrates and tethered reaction intermediates to efficiently channel substrates through its catalytic steps. With a total size of 5-12 MDa, PDHc is among the largest biomolecular assemblies. It consists of three enzymatic components acting sequentially: E1 (pyruvate dehydrogenase), E2 (dihydrolipoamide acetyltransferase), and E3 (dihydrolipoamide dehydrogenase). In eukaryotes, an additional E3-binding protein (E3BP) recruits E3 to the complex. E2 (and E3BP) subunits form the structural core, typically exhibiting octahedral or icosahedral symmetry, while E1 and E3 bind to the core as peripheral subunits. Advances in structural biology, particularly cryo-EM, X-ray crystallography, and nuclear magnetic resonance (NMR), have provided valuable insights into PDHc organization, assembly principles, and species-specific variation. Here, we review diverse PDHc architectures across phylogenetic groups. Understanding these structural and functional adaptations is essential for fully deciphering PDHc regulation and its role in metabolism.","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144845059","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

Development of visible light-sensitive human neuropsin (OPN5) via single amino acid substitution 通过单氨基酸取代制备可见光敏人神经素（OPN5）。

IF 3 4区生物学

FEBS Letters Pub Date : 2025-08-13 DOI: 10.1002/1873-3468.70130

Yusuke Sakai, Richard J. McDowell, Robert J. Lucas

引用次数: 0