Journal of Biological Chemistry最新文献_第8页

Cysteine redoxome landscape in the liver of male mice fed a high-fat high-sucrose diet. 高脂高糖饮食对雄性小鼠肝脏半胱氨酸氧化酶体的影响。

IF 4.8 2区生物学

Journal of Biological Chemistry Pub Date : 2025-09-16 DOI: 10.1016/j.jbc.2025.110730

Cynthia M Galicia-Medina,Hein Ko Oo,Takumi Nishiuchi,Ryota Tanida,Tuerdiguli Abuduyimiti,Hisanori Goto,Yujiro Nakano,Yumie Takeshita,Kiyo-Aki Ishii,Takashi Toyama,Yoshiro Saito,Hiroaki Takayama,Toshinari Takamura

{"title":"Cysteine redoxome landscape in the liver of male mice fed a high-fat high-sucrose diet.","authors":"Cynthia M Galicia-Medina,Hein Ko Oo,Takumi Nishiuchi,Ryota Tanida,Tuerdiguli Abuduyimiti,Hisanori Goto,Yujiro Nakano,Yumie Takeshita,Kiyo-Aki Ishii,Takashi Toyama,Yoshiro Saito,Hiroaki Takayama,Toshinari Takamura","doi":"10.1016/j.jbc.2025.110730","DOIUrl":"https://doi.org/10.1016/j.jbc.2025.110730","url":null,"abstract":"Reversible cysteine post-translational modifications serve as a \"switch\" for protein structure-function dynamics. Herein, we applied a comprehensive strategy to map the cysteine redoxome by pinpointing over 5,000 oxidized and reduced cysteine residues in the liver of male mice fed either a normal chow diet (NCD) or a high-fat/high-sucrose diet (HFHSD). The global and subcellular distribution of oxidized and reduced cysteine residues remained stable across both diet groups, indicating that HFHSD does not induce widespread shifts in cysteine redox equilibrium. Proteomic analyses revealed that HFHSD upregulates proteins involved in genomic stability, lipid detoxification, and energy regulation, while downregulating those linked to detoxification and metabolic flexibility. Notably, 169 cysteine residues exhibited dynamic redox changes in response to HFHSD, mapping to 35 KEGG pathways central to redox balance and energy homeostasis. Motif and structural analyses demonstrated that the reactivity of cysteine residues sensitive to redox stress is dictated by distinct electrostatic microenvironments and subcellular localization. Cysteine residues sensitive to HFHSD-induced oxidation were enriched in mitochondria and cytosol, and cysteine residues sensitive to HFHSD-induced reduction in extracellular regions. Furthermore, cysteine residues sensitive to HFHSD-induced reduction mainly participate in disulfide bond formation and are exposed to the surface of the protein, suggesting roles as molecular switches in protein function. The current cysteine redoxome strategy broadens the disease-associated proteome landscape and provides potential therapeutic target cysteine residues critical for regulating protein functions and interactions relevant to pathophysiology.","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":"78 1","pages":"110730"},"PeriodicalIF":4.8,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145083550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 serine protease HTRA1 targets Tau fibrils and provides a proteolytic barrier against pathogenic protein conformations. 丝氨酸蛋白酶HTRA1靶向Tau原纤维，并提供一种蛋白水解屏障来抵抗致病性蛋白构象。

IF 4.8 2区生物学

Journal of Biological Chemistry Pub Date : 2025-09-16 DOI: 10.1016/j.jbc.2025.110729

Birte Hagemeier,Kamilla Ripkens,Nina Schulze,Anika Bluemke,Michal Strzala,Michelle Koci,Farnusch Kaschani,Markus Kaiser,Michael Erkelenz,Sebastian Schluecker,Melisa Merdanovic,Simon Poepsel,Doris Hellerschmied,Steven G Burston,Michael Ehrmann

{"title":"The serine protease HTRA1 targets Tau fibrils and provides a proteolytic barrier against pathogenic protein conformations.","authors":"Birte Hagemeier,Kamilla Ripkens,Nina Schulze,Anika Bluemke,Michal Strzala,Michelle Koci,Farnusch Kaschani,Markus Kaiser,Michael Erkelenz,Sebastian Schluecker,Melisa Merdanovic,Simon Poepsel,Doris Hellerschmied,Steven G Burston,Michael Ehrmann","doi":"10.1016/j.jbc.2025.110729","DOIUrl":"https://doi.org/10.1016/j.jbc.2025.110729","url":null,"abstract":"Tauopathies such as Alzheimer's disease, frontotemporal dementia with Parkinsonism, and other neurodegenerative diseases are classified as protein folding diseases because they share amyloid fibrils as a hallmark. Typically, amyloid fibrils accumulate and spread through tissue over time. It is assumed that this process is accelerated as protein quality control becomes overwhelmed in aged tissues. However, a deep understanding of how specific protein quality control factors interfere with fibril accumulation and thereby delay disease onset is lacking. Here, we show that the widely conserved serine protease HTRA1 is activated by tau fibrils and provide quantitative, topological, and temporal insights into the proteolytic degradation of soluble and fibrillar tau. Live cell fluorescence microscopy demonstrates the interaction of HTRA1 with tau fibrils and their proteolytic degradation in cells. Our data highlight the potential of HTRA1 to act in a cell non-autonomous defense mechanism against the intercellular spread of pathogenic protein conformations.","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":"79 1","pages":"110729"},"PeriodicalIF":4.8,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145083553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 inhibitor of retinal membrane guanylyl cyclase suppresses cGMP synthesis in photoreceptors. 视网膜膜鸟苷环化酶蛋白抑制剂抑制光感受器中cGMP的合成。

IF 4.8 2区生物学

Journal of Biological Chemistry Pub Date : 2025-09-15 DOI: 10.1016/j.jbc.2025.110718

Igor V Peshenko,Elena V Olshevskaya,Alexander M Dizhoor

引用次数: 0

The Impact of pH on Proteolytic Activity in Wound Fluid: Implications for Acid Therapy. pH值对伤口液蛋白水解活性的影响：酸治疗的意义。

IF 4.8 2区生物学

Journal of Biological Chemistry Pub Date : 2025-09-15 DOI: 10.1016/j.jbc.2025.110723

Elany Barbosa da Silva,Meredith J Crane,Lawrence Liu,Danielle J Gelsinger,Alexander R D Jordon,Phuong Le,Jack G Haggett,Samuel A Myers,Robin L McKinney,Craig P Eberson,Amanda M Jamieson,Anthony J O'Donoghue

{"title":"The Impact of pH on Proteolytic Activity in Wound Fluid: Implications for Acid Therapy.","authors":"Elany Barbosa da Silva,Meredith J Crane,Lawrence Liu,Danielle J Gelsinger,Alexander R D Jordon,Phuong Le,Jack G Haggett,Samuel A Myers,Robin L McKinney,Craig P Eberson,Amanda M Jamieson,Anthony J O'Donoghue","doi":"10.1016/j.jbc.2025.110723","DOIUrl":"https://doi.org/10.1016/j.jbc.2025.110723","url":null,"abstract":"Wound healing necessitates a balance between synthesis and breakdown of extracellular matrix components, which is tightly regulated by proteases and their inhibitors. While studies have demonstrated that citric and acetic acid treatments enhance healing in recalcitrant wounds, the underlying proteolytic mechanisms remain elusive. In this study, we systematically evaluated changes in the proteolytic activity of murine wound fluid upon acidification. A library of 228 synthetic peptides served as reporters of protease activity at pH 7.4, pH 5.0 and pH 3.5. The peptide digestion patterns differed at each pH, revealing that proteases active at pH 7.4 are inactivated at pH 3.5. Notably, cathepsin D emerged as the dominant active enzyme at pH 3.5, and its activity was inhibited by pepstatin. Using a fluorogenic substrate, we quantified cathepsin D activity across varying pH levels and demonstrated optimal activity between pH 3.0 and 3.8. This activity was detectable as early as one day post-injury and persisted over the following ten days. Importantly, human wound fluid exhibited the same activity profile, validating the mouse model as a relevant system for studying acid-mediated wound healing processes.","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":"1 1","pages":"110723"},"PeriodicalIF":4.8,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145078284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 cytoplasmic domains of the CNNM family of transmembrane proteins modulate the ion channel-kinase TRPM7. 跨膜蛋白CNNM家族的细胞质结构域调节离子通道激酶TRPM7。

IF 4.8 2区生物学

Journal of Biological Chemistry Pub Date : 2025-09-15 DOI: 10.1016/j.jbc.2025.110720

Sandra Tetteh,Pengyu Zong,Jianlin Feng,Emma L Lee,Namariq Al-Saadi,Jeremy Willekens,Ayush Shah,Thushara Nethramangalath,Abigail L Galeano,Haiyen Zheng,Kalle Gehring,Lixia Yue,Loren W Runnels

{"title":"The cytoplasmic domains of the CNNM family of transmembrane proteins modulate the ion channel-kinase TRPM7.","authors":"Sandra Tetteh,Pengyu Zong,Jianlin Feng,Emma L Lee,Namariq Al-Saadi,Jeremy Willekens,Ayush Shah,Thushara Nethramangalath,Abigail L Galeano,Haiyen Zheng,Kalle Gehring,Lixia Yue,Loren W Runnels","doi":"10.1016/j.jbc.2025.110720","DOIUrl":"https://doi.org/10.1016/j.jbc.2025.110720","url":null,"abstract":"The ion channel and kinase TRPM7 contributes to a wide range of physiological and pathological processes, yet how it is controlled by signaling pathways remains poorly understood. Members of the CNNM family of transmembrane proteins (CNNM1-4) have been shown to selectively bind and regulate the TRPM7 channel. CNNM binding partners, including the PRL family of proteins (PRL1-3) and ARL15, also modulate TRPM7 channel function. However, the regulation of TRPM7's kinase activity in vivo remains unclear. CNNMs contain a DUF21 transmembrane domain, a CBS-pair domain, followed by a COOH-terminal CNBH domain. Here, we identified multiple interaction sites between TRPM7 and CNNMs. The CNNM transmembrane domain was sufficient to mediate assembly of the CNNM2-TRPM7 complex, while the CBS-pair and CNBH domains provided additional points of contact. Electrophysiological analysis revealed that the CBS-pair domain modulates TRPM7 channel activity. ARL15, a known suppressor of TRPM7 channel function, required the CNNM CBS-pair domain to inhibit channel activity. Additionally, the CNNM2 CNBH domain bound to the TRPM7 kinase domain and modestly enhanced its catalytic activity in vitro. Collectively, these findings demonstrate that the cytoplasmic domains of CNNMs play critical roles in regulating TRPM7 channel and kinase activities.","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":"30 1","pages":"110720"},"PeriodicalIF":4.8,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145078278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 RING-finger domain of Arabidopsis RMR functions as an E3 ligase essential for post-Golgi trafficking. 拟南芥RMR的RING-finger结构域在高尔基转运中起E3连接酶的作用。

IF 4.8 2区生物学

Journal of Biological Chemistry Pub Date : 2025-09-15 DOI: 10.1016/j.jbc.2025.110721

Shuai Chen,Yonglun Zeng,Hiu Yan Wong,Yihong Chen,Lei Yang,Fang Luo,Caiji Gao,Liwen Jiang,Kam-Bo Wong

{"title":"The RING-finger domain of Arabidopsis RMR functions as an E3 ligase essential for post-Golgi trafficking.","authors":"Shuai Chen,Yonglun Zeng,Hiu Yan Wong,Yihong Chen,Lei Yang,Fang Luo,Caiji Gao,Liwen Jiang,Kam-Bo Wong","doi":"10.1016/j.jbc.2025.110721","DOIUrl":"https://doi.org/10.1016/j.jbc.2025.110721","url":null,"abstract":"Receptor-homology-transmembrane-RING-H2 (RMR) sorting receptors are essential for directing soluble cargo proteins to protein storage vacuoles in plants. These type I integral membrane proteins comprise a single transmembrane domain, an N-terminal lumenal region containing a protease-associated domain for cargo recognition, and a C-terminal cytoplasmic region (CT) with a Really-Interesting-New-Gene-H2 (RING-H2) domain. Here, we determined the crystal structure of the RING-H2 domain of Arabidopsis RMR isoform-1 (AtRMR1-RING), where the conserved C3H2C3 motif coordinates two Zn ions, a feature typical of RING-type E3 ligases. AtRMR1-RING was shown to interact with Arabidopsis E2 ubiquitin-conjugating enzyme, and exhibits E3 ligase activity in an in vitro ubiquitination assay. Biochemical analysis reveals that I234Y substitution disrupted the E2/E3 interaction and greatly reduced E3 ligase activity. Furthermore, we showed that the conserved RING-H2 domains of AtRMR isoform 2, 3 and 4 are also E3 ligases. Inactivation of E3 ligase activity by the I234Y mutation resulted in Golgi retention of AtRMR1-CT and AtRMR2. These findings suggest that the E3 ligase activity is essential for post-Golgi trafficking of RMR receptors, providing new insights into receptor-mediated protein sorting in plants.","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":"1 1","pages":"110721"},"PeriodicalIF":4.8,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145078280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

DUF-721 and N-terminal extension of the helicase loader DciA bind ssDNA to promote replicative DnaB helicase loading in Caulobacter crescentus. DUF-721和解旋酶装载器DciA的n端延伸结合ssDNA，促进新月茎杆菌的复制性dna解旋酶装载。

IF 4.8 2区生物学

Journal of Biological Chemistry Pub Date : 2025-09-15 DOI: 10.1016/j.jbc.2025.110724

Keito Watanabe,Shohei Sato,Naoto Itani,Dengyu Wang,Nanato Kiyohara,Satoshi Matsuoka,Tsutomu Katayama,Shogo Ozaki

{"title":"DUF-721 and N-terminal extension of the helicase loader DciA bind ssDNA to promote replicative DnaB helicase loading in Caulobacter crescentus.","authors":"Keito Watanabe,Shohei Sato,Naoto Itani,Dengyu Wang,Nanato Kiyohara,Satoshi Matsuoka,Tsutomu Katayama,Shogo Ozaki","doi":"10.1016/j.jbc.2025.110724","DOIUrl":"https://doi.org/10.1016/j.jbc.2025.110724","url":null,"abstract":"The establishment of replication forks relies on a dedicated molecular system by which a ring-shaped replicative DNA helicase is loaded onto the chromosome DNA, facilitating the unwinding of duplex DNA into single-stranded DNA. In most bacteria, the DnaB helicase coevolved with its accessory protein DciA loader, a member of the domain of unknown function (DUF)-721-containing protein family. In the model bacterium Caulobacter crescentus, DciA promotes helicase loading and the C-terminal extension of DUF-721 serves as a specific binding site for the cognate DnaB helicase. However, the mechanistic role of DUF-721 in DnaB helicase loading remains unknown. Here, we provide evidence that the ssDNA binding activity of DUF-721 is crucial for DnaB helicase loading in C. crescentus. Using plasmid complementation assays, we identified DciA Arg106 and Leu119 in DUF-721 as essential residues for in vivo DciA functions. Biochemical analyses revealed that both residues are essential for helicase loading in vitro. Specifically, Arg106 is important for ssDNA binding, with this activity being supported directly or indirectly by Leu119. Yet, these residues are dispensable for DnaB binding. Additionally, we reveal the N-terminal extension of DUE-721 is crucial for ssDNA binding and helicase loading. Given the conservation of Arg106 and Leu119 among DciA family proteins, these results suggest that ssDNA binding via DciA DUF-721 domain plays a specific and conserved role in helicase loading. Providing a molecular insight into how DciA stimulates helicase loading, our findings highlight a conserved mechanism of ssDNA binding among DciA-family proteins.","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":"38 1","pages":"110724"},"PeriodicalIF":4.8,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145078179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

USP52 inhibits cell ferroptosis via Hippo/YAP pathway and blocks immunotherapy in colorectal cancer. USP52通过Hippo/YAP途径抑制细胞铁下垂，阻断结直肠癌的免疫治疗。

IF 4.8 2区生物学

Journal of Biological Chemistry Pub Date : 2025-09-15 DOI: 10.1016/j.jbc.2025.110725

Jingkai Zhou,Haihang Nie,Chenhui Liu,Lu Ding,Ting Zheng,Li Du,Yali Yu,Yuntian Hong,Chao Yang,Qiu Zhao,Meng Zhang,Haizhou Wang,Fan Wang

{"title":"USP52 inhibits cell ferroptosis via Hippo/YAP pathway and blocks immunotherapy in colorectal cancer.","authors":"Jingkai Zhou,Haihang Nie,Chenhui Liu,Lu Ding,Ting Zheng,Li Du,Yali Yu,Yuntian Hong,Chao Yang,Qiu Zhao,Meng Zhang,Haizhou Wang,Fan Wang","doi":"10.1016/j.jbc.2025.110725","DOIUrl":"https://doi.org/10.1016/j.jbc.2025.110725","url":null,"abstract":"Colorectal cancer (CRC) is one of the most prevalent malignancies in humans. Understanding its molecular mechanisms to guide clinical management is crucial. Ferroptosis represents a novel form of regulated cell death that is characterized by highly iron-dependent lipid peroxidation. Despite growing interest, the roles and vulnerabilities determining ferroptosis sensitivity in CRC remain unclear. In this study, we identified Ubiquitin Specific Peptidase 52 (USP52) as a specific deubiquitinating enzyme of yes-associated protein (YAP) in CRC, which could stabilize YAP by removing the K11-linked ubiquitin chains. USP52 knockdown decreased the expression of YAP protein and its target gene (CTGF, CYR61). Through a series of comprehensive in vivo and in vitro experiments, we proved that USP52 promoted CRC cells proliferation, migration, and invasion and attenuated the sensitivity of CRC cells to ferroptosis. Notably, USP52 inhibition retarded tumor growth and enhanced CD8+ T cell infiltration, which potentiated tumor response to anti-PD-L1 immunotherapy in vivo. In general, our research uncovered that USP52 suppressed ferroptosis through the Hippo/YAP signaling and highlighted targeting USP52 as a potential therapeutic strategy to boost ferroptosis for enhancing cancer immunotherapy.","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":"79 1","pages":"110725"},"PeriodicalIF":4.8,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145078182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Structure-Based Identification of Salvianolic Acid B as an Inhibitor Targeting Salmonella InvC ATPase. 基于结构的沙门氏菌InvC atp酶抑制剂丹酚酸B的鉴定

IF 4.8 2区生物学

Journal of Biological Chemistry Pub Date : 2025-09-15 DOI: 10.1016/j.jbc.2025.110722

Jiayang Liu,Xinyou Zhang,Kaiyao Zhang,Jianfeng Wang,Xuming Deng,Hongtao Liu,Yanhong Deng,Jiazhang Qiu

{"title":"Structure-Based Identification of Salvianolic Acid B as an Inhibitor Targeting Salmonella InvC ATPase.","authors":"Jiayang Liu,Xinyou Zhang,Kaiyao Zhang,Jianfeng Wang,Xuming Deng,Hongtao Liu,Yanhong Deng,Jiazhang Qiu","doi":"10.1016/j.jbc.2025.110722","DOIUrl":"https://doi.org/10.1016/j.jbc.2025.110722","url":null,"abstract":"Multidrug-resistant (MDR) Salmonella poses a significant global health threat. The Type III Secretion System 1 (T3SS-1) and its ATPase InvC are crucial for virulence and promising drug targets. Through structure-based virtual screening, we identified Salvianolic acid B (SA-B) as an inhibitor of InvC. To rigorously characterize its interaction, we performed extensive molecular dynamics simulations, which revealed a 'dynamic yet stable' binding mode within the ATP-binding pocket. Subsequent experimental validation confirmed SA-B directly binds the InvC ATP pocket and inhibits its ATPase activity. Consequently, SA-B inhibited T3SS-1-mediated effector secretion and reduced the invasion of host cells by S. Typhimurium in vitro, without affecting bacterial viability. Importantly, SA-B demonstrated significant therapeutic efficacy in Galleria mellonella and mouse infection models, improving survival and reducing bacterial burden. This study establishes SA-B as a promising anti-virulence lead compound targeting Salmonella InvC, offering a strategy that may mitigate antibiotic resistance by selectively disarming pathogen virulence mechanisms rather than targeting viability.","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":"28 1","pages":"110722"},"PeriodicalIF":4.8,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145078281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 complete λ-carrageenan depolymerization cascade from a marine Pseudoalteromonad revealed by structural analysis of the enzymes. 通过对酶的结构分析，揭示了一种海洋假异交单胞菌的完整λ-卡拉胶解聚级联反应。

IF 4 2区生物学

Journal of Biological Chemistry Pub Date : 2025-09-15 DOI: 10.1016/j.jbc.2025.110719

Chelsea J Vickers, Andrew G Hettle, Joanne K Hobbs, Sarah Shapiro-Ward, Benjamin Pluvinage, Brendon J Medley, Bailey E McGuire, Liam Mihalynuk, Nitin Nitin, Wesley F Zandberg, Alisdair B Boraston

{"title":"The complete λ-carrageenan depolymerization cascade from a marine Pseudoalteromonad revealed by structural analysis of the enzymes.","authors":"Chelsea J Vickers, Andrew G Hettle, Joanne K Hobbs, Sarah Shapiro-Ward, Benjamin Pluvinage, Brendon J Medley, Bailey E McGuire, Liam Mihalynuk, Nitin Nitin, Wesley F Zandberg, Alisdair B Boraston","doi":"10.1016/j.jbc.2025.110719","DOIUrl":"https://doi.org/10.1016/j.jbc.2025.110719","url":null,"abstract":"<p><p>Carrageenans are a complex group of polysaccharides derived from the cell walls of red macroalgae. They are an abundant, yet recalcitrant nutrient source for most marine heterotrophic bacteria. Some member species of the Pseudoalteromonas genus are effective at metabolizing carrageenan. However, the enzymatic pathway for λ-carrageenan, one of the most sulfated naturally occurring polysaccharides, remains unknown. Using detailed structural analysis by X-ray crystallography we reveal the sophisticated and cyclic enzymatic cascade deployed by Pseudoalteromonas distincta (strain U2A) to utilize λ-carrageenan. The cascade incorporates ten glycoside hydrolases and five sulfatases that are specific for λ-carrageenan and cooperate to completely deconstruct this polysaccharide, thus yielding galactose monosaccharides for subsequent energy production. The detailed molecular understanding of λ-carrageenan depolymerisation provided includes structural evidence for a lesser described sulfatase catalytic mechanism and elucidation of a distinct catabolic cascade that is unique from previously described carrageenan metabolic pathways. This insight also holds potential for the application of enzymatic logic in the generation of high value products from abundant natural biopolymers, such as carrageenans.</p>","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":" ","pages":"110719"},"PeriodicalIF":4.0,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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