Biochemical Journal最新文献_第6页

Specialized killing across the domains of life by the type VI secretion systems of Pseudomonas aeruginosa. 通过铜绿假单胞菌的VI型分泌系统在生命的各个领域进行专门杀伤。

IF 4.4 3区生物学

Biochemical Journal Pub Date : 2025-01-08 DOI: 10.1042/BCJ20230240

Jake Colautti, Steven D Kelly, John C Whitney

{"title":"Specialized killing across the domains of life by the type VI secretion systems of Pseudomonas aeruginosa.","authors":"Jake Colautti, Steven D Kelly, John C Whitney","doi":"10.1042/BCJ20230240","DOIUrl":"10.1042/BCJ20230240","url":null,"abstract":"Type VI secretion systems (T6SSs) are widespread bacterial protein secretion machines that inject toxic effector proteins into nearby cells, thus facilitating both bacterial competition and virulence. Pseudomonas aeruginosa encodes three evolutionarily distinct T6SSs that each export a unique repertoire of effectors. Owing to its genetic tractability, P. aeruginosa has served as a model organism for molecular studies of the T6SS. However, P. aeruginosa is also an opportunistic pathogen and ubiquitous environmental organism that thrives in a wide range of habitats. Consequently, studies of its T6SSs have provided insight into the role these systems play in the diverse lifestyles of this species. In this review, we discuss recent advances in understanding the regulation and toxin repertoire of each of the three P. aeruginosa T6SSs. We argue that these T6SSs serve distinct physiological functions; whereas one system is a dedicated defensive weapon for interbacterial antagonism, the other two T6SSs appear to function primarily during infection. We find support for this model in examining the signalling pathways that control the expression of each T6SS and co-ordinate the activity of these systems with other P. aeruginosa behaviours. Furthermore, we discuss the effector repertoires of each T6SS and connect the mechanisms by which these effectors kill target cells to the ecological conditions under which their respective systems are activated. Understanding the T6SSs of P. aeruginosa in the context of this organism's diverse lifestyles will provide insight into the physiological roles these secretion systems play in this remarkably adaptable bacterium.","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":"482 1","pages":"1-15"},"PeriodicalIF":4.4,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142943579","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

The MYO1B and MYO5B motor proteins and the sorting nexin SNX27 regulate apical targeting of membrane mucin MUC17 in enterocytes. MYO1B和MYO5B运动蛋白以及分选连接蛋白SNX27调控肠细胞中膜黏液蛋白MUC17的顶端靶向。

IF 4.4 3区生物学

Biochemical Journal Pub Date : 2025-01-08 DOI: 10.1042/BCJ20240204

Sofia Jäverfelt, Gustaf Hellsén, Izumi Kaji, James R Goldenring, Thaher Pelaseyed

{"title":"The MYO1B and MYO5B motor proteins and the sorting nexin SNX27 regulate apical targeting of membrane mucin MUC17 in enterocytes.","authors":"Sofia Jäverfelt, Gustaf Hellsén, Izumi Kaji, James R Goldenring, Thaher Pelaseyed","doi":"10.1042/BCJ20240204","DOIUrl":"10.1042/BCJ20240204","url":null,"abstract":"A dense glycocalyx, composed of the megaDalton-sized membrane mucin MUC17, coats the microvilli in the apical brush border of transporting intestinal epithelial cells, called enterocytes. The formation of the MUC17-based glycocalyx in the mouse small intestine occurs at the critical suckling-weaning transition. The glycocalyx extends 1 µm into the intestinal lumen and prevents the gut bacteria from directly attaching to the enterocytes. To date, the mechanism behind the positioning of MUC17 to the brush border is not known. Here, we show that the actin-based motor proteins MYO1B and MYO5B, and the sorting nexin SNX27, regulate apical targeting of MUC17 in enterocytes. We demonstrate that MUC17 turnover at the brush border is slow and controlled by MYO1B and SNX27. Furthermore, we report that MYO1B regulates MUC17 protein levels in enterocytes, whereas MYO5B specifically governs MUC17 levels at the brush border. Together, our results extend our understanding of the apical targeting of membrane mucins and provide mechanistic insights into how defective positioning of MUC17 renders enterocytes sensitive to bacterial challenges.","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":" ","pages":"1-23"},"PeriodicalIF":4.4,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805927","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

Loss of peroxiredoxin 6 alters lipid composition and distribution resulting in increased sensitivity to ferroptosis. 过氧化物歧化酶 6 (PRDX6) 的缺失会改变脂质的组成和分布，从而增加对铁中毒的敏感性。

IF 4.4 3区生物学

Biochemical Journal Pub Date : 2024-12-23 DOI: 10.1042/BCJ20240445

Daniel J Lagal, Ángel Ortiz-Alcántara, José R Pedrajas, Brian McDonagh, J Antonio Bárcena, Raquel Requejo-Aguilar, C Alicia Padilla

{"title":"Loss of peroxiredoxin 6 alters lipid composition and distribution resulting in increased sensitivity to ferroptosis.","authors":"Daniel J Lagal, Ángel Ortiz-Alcántara, José R Pedrajas, Brian McDonagh, J Antonio Bárcena, Raquel Requejo-Aguilar, C Alicia Padilla","doi":"10.1042/BCJ20240445","DOIUrl":"10.1042/BCJ20240445","url":null,"abstract":"Peroxiredoxin 6 (PRDX6) is a multifunctional enzyme involved in phospholipid peroxide repair and metabolism. In this study we investigated the global lipid composition of a human hepatocarcinoma cell line SNU475 lacking PRDX6 and lipid related cellular processes. There was a general decrease in multiple lipids species upon loss of PRDX6, in particular sphingomyelins and acylcarnitines, consistent with previously observed alterations in cell signaling pathways and mitochondrial dysfunction. Deprivation of docosahexaenoic acid and related species was also evident. However, a few striking exceptions are worth highlighting: (1) Three specific arachidonic acid (AA) containing phophatidylcholines (PC) increased significantly. The increase of sn1-stearic/sn2-PUFA containing PC and sn2-AA containing plasmenyls are indicative of a preference of PRDX6 iPLA2 activity for these AA storage glycerophospholipids. (2) Several polyunsaturated fatty acids (PUFA) and PUFA containing triacylglycerols accumulated together with increased formation of lipid droplets, an indication of altered FA flux and PUFA sequestration in PRDX6 knockout cells. Loss of PRDX6 resulted in increased sensitivity to erastin-induced ferroptosis, independent of selenium and GPX4, as a consequence of increased levels of lipid hydroperoxides, that reverted to normal levels upon rescue with PRDX6. The results presented demonstrate that all three enzymatic activities of PRDX6 contribute to the role of this multifunctional enzyme in diverse cellular processes, including membrane phospholipid remodeling and glycerophospholipid functional diversity, resulting in altered lipid peroxides and modulation of AA disposition and traffic. These contributions highlight the complexity of the changes that loss of PRDX6 exerts on cell functionality.","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":" ","pages":"1997-2015"},"PeriodicalIF":4.4,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11668489/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Tweaking the redox properties of PpcA from Geobacter metallireducens with protein engineering. 用蛋白质工程技术调节金属还原杆菌PpcA的氧化还原特性。

IF 4.4 3区生物学

Biochemical Journal Pub Date : 2024-12-23 DOI: 10.1042/BCJ20240423

Pilar C Portela, Marta A Silva, Alexandre Almeida, Gonçalo F Damas, Carlos A Salgueiro

{"title":"Tweaking the redox properties of PpcA from Geobacter metallireducens with protein engineering.","authors":"Pilar C Portela, Marta A Silva, Alexandre Almeida, Gonçalo F Damas, Carlos A Salgueiro","doi":"10.1042/BCJ20240423","DOIUrl":"10.1042/BCJ20240423","url":null,"abstract":"Geobacter's unique ability to perform extracellular electron transfer (EET) to electrodes in microbial fuel cells (MFCs) has sparked the implementation of sustainable production of electrical energy. However, the electrochemical performance of Geobacter's biofilms in MFCs remains challenging to implement industrially. Multiple approaches are being investigated to enhance MFC technologies. Protein engineering of multihaem cytochromes, key components of Geobacter's EET pathways, can, conceivably, be pursued to improve the EET chain. The periplasmic cytochrome PpcA bridges ET from the inner to the outer membrane and its deletion impairs this crucial step. The functional characterisation of PpcA homologues from Geobacter sulfurreducens (Gs) and Geobacter metallireducens (Gm) revealed a significantly different redox behaviour even though they only differ by thirteen amino acids. In a previous study, we found that the single replacement of a tryptophan residue by methionine (W45M) in PpcAGm shifted the reduction potential value 33% towards that of PpcAGs. In this work, we expanded our investigation to include other non-conserved residues by conducting five mutation rounds. We identified the most relevant residues controlling the redox properties of PpcAGm. With just four mutations (K19, G25, N26, W45) the reduction potential value of PpcAGm was shifted 71% toward that of PpcAGs. Additionally, in the quadruple mutant, it was possible to replicate the haem oxidation order and the functional mechanisms of PpcAGs, which differ from those in PpcAGm. Overall, the mutants exhibit diverse redox and functional mechanisms that could be explored as a library for the future design of minimal, synthetic, ET chains in Geobacter.","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":" ","pages":"2017-2036"},"PeriodicalIF":4.4,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765734","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

The open to closed D-loop conformational switch determines length in filopodia-like actin bundles. 打开到闭合的d环构象开关决定了丝状伪足样肌动蛋白束的长度。

IF 4.4 3区生物学

Biochemical Journal Pub Date : 2024-12-23 DOI: 10.1042/BCJ20240367

Jonathan R Gadsby, Pantelis Savvas Ioannou, Richard Butler, Julia Mason, Alison J Smith, Ulrich Dobramysl, Stacey E Chin, Claire Dobson, Jennifer L Gallop

{"title":"The open to closed D-loop conformational switch determines length in filopodia-like actin bundles.","authors":"Jonathan R Gadsby, Pantelis Savvas Ioannou, Richard Butler, Julia Mason, Alison J Smith, Ulrich Dobramysl, Stacey E Chin, Claire Dobson, Jennifer L Gallop","doi":"10.1042/BCJ20240367","DOIUrl":"10.1042/BCJ20240367","url":null,"abstract":"Filopodia, microspikes and cytonemes are implicated in sensing the environment and in dissemination of morphogens, organelles and pathogens across tissues. Their major structural component is parallel bundles of actin filaments that assemble from the cell membrane. Whilst the length of filopodia is central to their function, it is not known how their lengths are determined by actin bundle dynamics. Here, we identified a set of monoclonal antibodies that lengthen filopodia-like structures formed in a cell-free reconstitution system, and used them to uncover a key molecular switch governing length regulation. Using immunolabelling, enzyme-linked immunosorbent assays, immunoprecipitation and immunoblock experiments, we identified four antibodies that lengthen actin bundles by selectively binding the open DNase 1-binding loop (D-loop) of actin filaments. The antibodies inhibit actin disassembly and their effects can be alleviated by providing additional actin or cofilin. This work indicates that maintaining an open state of the actin filament D-loop is a mechanism of generating long filopodia-like actin bundles.","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":" ","pages":"1977-1995"},"PeriodicalIF":4.4,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11668490/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Development of circadian rhythms in mammalian systems. 哺乳动物生理节律的发展。

IF 4.4 3区生物学

Biochemical Journal Pub Date : 2024-12-23 DOI: 10.1042/BCJ20210060

Junghyun Lee, Sevde Goker, Sookkyung Lim, Christian I Hong

引用次数: 0

Gα12 and Gα13 proteins are required for transforming growth factor-β-induced myofibroblast differentiation. TGF-β诱导的肌成纤维细胞分化需要Ga12和Ga13蛋白。

IF 4.4 3区生物学

Biochemical Journal Pub Date : 2024-12-18 DOI: 10.1042/BCJ20240317

Eleanor B Reed, Albert Sitikov, Kun Woo D Shin, Robert B Hamanaka, Rengül Cetin-Atalay, Gökhan M Mutlu, Alexander A Mongin, Nickolai O Dulin

{"title":"Gα12 and Gα13 proteins are required for transforming growth factor-β-induced myofibroblast differentiation.","authors":"Eleanor B Reed, Albert Sitikov, Kun Woo D Shin, Robert B Hamanaka, Rengül Cetin-Atalay, Gökhan M Mutlu, Alexander A Mongin, Nickolai O Dulin","doi":"10.1042/BCJ20240317","DOIUrl":"10.1042/BCJ20240317","url":null,"abstract":"Myofibroblast differentiation, characterized by accumulation of cytoskeletal and extracellular matrix proteins by fibroblasts, is a key process in wound healing and pathogenesis of tissue fibrosis. Transforming growth factor-β (TGF-β) is the most powerful known driver of myofibroblast differentiation. TGF-β signals through transmembrane receptor serine/threonine kinases that phosphorylate Smad transcription factors (Smad2/3) leading to activation of transcription of target genes. Heterotrimeric G proteins mediate distinct signaling from seven-transmembrane G protein coupled receptors, which are not known to be linked to Smad activation. We tested whether G protein signaling plays any role in TGF-β-induced myofibroblast differentiation, using primary cultured human lung fibroblasts. Activation of Gαs by cholera toxin blocked TGF-β-induced myofibroblast differentiation without affecting Smad2/3 phosphorylation. Neither inhibition of Gαi by pertussis toxin nor siRNA-mediated combined knockdown of Gαq and Gα11 had a significant effect on TGF-β-induced myofibroblast differentiation. In contrast, combined knockdown of Gα12 and Gα13 significantly inhibited TGF-β-stimulated expression of myofibroblast marker proteins (collagen-1, fibronectin, smooth-muscle α-actin), with siGα12 being significantly more potent than siGα13. Mechanistically, combined knockdown of Gα12 and Gα13 resulted in substantially reduced phosphorylation of Smad2 and Smad3 in response to TGF-β, which was accompanied by a significant decrease in the expression of TGF-β receptors (TGFBR1, TGFBR2) and of Smad3. Thus, our study uncovers a novel role of Gα12/13 proteins in the control of TGF-β signaling and myofibroblast differentiation.","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":" ","pages":"1937-1948"},"PeriodicalIF":4.4,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11668492/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Opposing regulation of endoplasmic reticulum retention under stress by ERp44 and PDIA6. 应激下ERp44和PDIA6对内质网保留的反向调控。

IF 4.4 3区生物学

Biochemical Journal Pub Date : 2024-12-18 DOI: 10.1042/BCJ20240444

Olaya Yassin, Bellam Praveen, Odai Darawshi, Thomas LaFramboise, Miriam Shmuel, Shakti P Pattanayak, Brian K Law, Maria Hatzoglou, Boaz Tirosh

{"title":"Opposing regulation of endoplasmic reticulum retention under stress by ERp44 and PDIA6.","authors":"Olaya Yassin, Bellam Praveen, Odai Darawshi, Thomas LaFramboise, Miriam Shmuel, Shakti P Pattanayak, Brian K Law, Maria Hatzoglou, Boaz Tirosh","doi":"10.1042/BCJ20240444","DOIUrl":"10.1042/BCJ20240444","url":null,"abstract":"Conditions of endoplasmic reticulum (ER) stress reduce protein synthesis by provoking translation regulation, governed by the eIF2α kinase PERK. When PERK is inhibited during ER stress, retention of a selective subset of glycoproteins occurs, a phenomenon we termed selective ER retention (sERr). sERr clients are enriched with tyrosine kinase receptors (RTKs), which form large molecular weight disulfide bonded complexes in the ER. The protein disulfide isomerase ERp44 promotes sERr and increases the size of sERr complexes. Here we show that sERr is reversible upon washout. Pulse chase analyses show that upon recovery, only a small fraction of the sERr complexes disintegrates and contributes to the matured proteins, while most are newly synthesized. Sequential inductions of sERr and washouts demonstrate an accelerated recovery that is dependent on the unfolded protein response transducer IRE1. Since IRE1 regulates the expression level PDIA6, we analyzed its contribution to sERr. We found that PDIA6 and ERp44 constitutively interact by disulfides and have opposite effects on resumed recovery of trafficking following removal of sERr conditions. Deletion of ERp44 accelerates, while deletion of PDIA6 slows down recovery with a minimal effect on total protein synthesis. ERp44 is a primary interactor with sERr clients. When missing, PDIA6 partitions more into sERr complexes. Deletion of the tumor suppressor PTEN, which induces RTK signaling, promoted sERr formation kinetics, and accelerated the recovery, suggesting feedback between RTKs signaling and sERr. This study suggests that sERr, should develop physiologically or pathologically, is counteracted by adaptation responses that involve IRE1 and PDIA6.","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":" ","pages":"1921-1935"},"PeriodicalIF":4.4,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765778","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

On the function of TRAP substrate-binding proteins: the isethionate-specific binding protein IseP. 关于 TRAP 底物结合蛋白的功能：异蛋氨酸特异性结合蛋白 IseP。

IF 4.4 3区生物学

Biochemical Journal Pub Date : 2024-12-18 DOI: 10.1042/BCJ20240540

Michael C Newton-Vesty, Michael J Currie, James S Davies, Santosh Panjikar, Ashish Sethi, Andrew E Whitten, Zachary D Tillett, David M Wood, Joshua D Wright, Michael J Love, Timothy M Allison, Sam A Jamieson, Peter D Mace, Rachel A North, Renwick C J Dobson

{"title":"On the function of TRAP substrate-binding proteins: the isethionate-specific binding protein IseP.","authors":"Michael C Newton-Vesty, Michael J Currie, James S Davies, Santosh Panjikar, Ashish Sethi, Andrew E Whitten, Zachary D Tillett, David M Wood, Joshua D Wright, Michael J Love, Timothy M Allison, Sam A Jamieson, Peter D Mace, Rachel A North, Renwick C J Dobson","doi":"10.1042/BCJ20240540","DOIUrl":"10.1042/BCJ20240540","url":null,"abstract":"Bacteria evolve mechanisms to compete for limited resources and survive in new niches. Here we study the mechanism of isethionate import from the sulfate-reducing bacterium Oleidesulfovibrio alaskensis. The catabolism of isethionate by Desulfovibrio species has been implicated in human disease, due to hydrogen sulfide production, and has potential for industrial applications. O. alaskensis employs a tripartite ATP-independent periplasmic (TRAP) transporter (OaIsePQM) to import isethionate, which relies on the substrate-binding protein (OaIseP) to scavenge isethionate and deliver it to the membrane transporter component (OaIseQM) for import into the cell. We determined the binding affinity of isethionate to OaIseP by isothermal titration calorimetry, KD = 0.95 µM (68% CI = 0.6-1.4 µM), which is weaker compared with other TRAP substrate-binding proteins. The X-ray crystal structures of OaIseP in the ligand-free and isethionate-bound forms were obtained and showed that in the presence of isethionate, OaIseP adopts a closed conformation whereby two domains of the protein fold over the substrate. We serendipitously discovered two crystal forms with sulfonate-containing buffers (HEPES and MES) bound in the isethionate-binding site. However, these do not evoke domain closure, presumably because of the larger ligand size. Together, our data elucidate the molecular details of how a TRAP substrate-binding protein binds a sulfonate-containing substrate, rather than a typical carboxylate-containing substrate. These results may inform future antibiotic development to target TRAP transporters and provide insights into protein engineering of TRAP transporter substrate-binding proteins.","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":" ","pages":"1901-1920"},"PeriodicalIF":4.4,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11668362/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Ubiquitin E3 ligases in the plant Arg/N-degron pathway. 植物Arg/N-degron通路中的泛素E3连接酶。

IF 4.4 3区生物学

Biochemical Journal Pub Date : 2024-12-18 DOI: 10.1042/BCJ20240132

Keely E A Oldham, Peter D Mabbitt

{"title":"Ubiquitin E3 ligases in the plant Arg/N-degron pathway.","authors":"Keely E A Oldham, Peter D Mabbitt","doi":"10.1042/BCJ20240132","DOIUrl":"10.1042/BCJ20240132","url":null,"abstract":"Regulation of protein longevity via the ubiquitin (Ub) - proteasome pathway is fundamental to eukaryotic biology. Ubiquitin E3 ligases (E3s) interact with substrate proteins and provide specificity to the pathway. A small subset of E3s bind to specific exposed N-termini (N-degrons) and promote the ubiquitination of the bound protein. Collectively these E3s, and other N-degron binding proteins, are known as N-recognins. There is considerable functional divergence between fungi, animal, and plant N-recognins. In plants, at least three proteins (PRT1, PRT6, and BIG) participate in the Arg/N-degron pathway. PRT1 has demonstrated E3 ligase activity, whereas PRT6 and BIG are candidate E3s. The Arg/N-degron pathway plays a central role in plant development, germination, and submersion tolerance. The pathway has been manipulated both to improve crop performance and for conditional protein degradation. A more detailed structural and biochemical understanding of the Arg/N-recognins and their substrates is required to fully realise the biotechnological potential of the pathway. This perspective focuses on the structural and molecular details of substrate recognition and ubiquitination in the plant Arg/N-degron pathway. While PRT1 appears to be plant specific, the PRT6 and BIG proteins are similar to UBR1 and UBR4, respectively. Analysis of the cryo-EM structures of Saccharomyces UBR1 suggests that the mode of ubiquitin conjugating enzyme (E2) and substrate recruitment is conserved in PRT6, but regulation of the two N-recognins may be significantly different. The structurally characterised domains from human UBR4 are also likely to be conserved in BIG, however, there are sizeable gaps in our understanding of both proteins.","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":"481 24","pages":"1949-1965"},"PeriodicalIF":4.4,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11668491/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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