Journal of Biological Chemistry最新文献_第9页

Antimicrobial Peptides Selectively Target Malaria Parasites by a Cholesterol-Dependent Mechanism.

IF 4 2区生物学

Journal of Biological Chemistry Pub Date : 2025-02-17 DOI: 10.1016/j.jbc.2025.108298

Edo Kiper, Daniel Ben Hur, Daniel Alfandari, Abel Cruz Camacho, Naiem Ahmad Wani, Gal David Efrat, Mattia I Morandi, Moshe Goldsmith, Ron Rotkopf, Roman Kamyshinsky, Arunaditya Deshmukh, Nur Elyza Binte Zulkifli, Navid Asmari, Marcos Penedo, Georg Fantner, Ziv Porat, Ido Azuri, Irit Rosenhek-Goldian, Chetan E Chitnis, Yechiel Shai, Neta Regev-Rudzki

{"title":"Antimicrobial Peptides Selectively Target Malaria Parasites by a Cholesterol-Dependent Mechanism.","authors":"Edo Kiper, Daniel Ben Hur, Daniel Alfandari, Abel Cruz Camacho, Naiem Ahmad Wani, Gal David Efrat, Mattia I Morandi, Moshe Goldsmith, Ron Rotkopf, Roman Kamyshinsky, Arunaditya Deshmukh, Nur Elyza Binte Zulkifli, Navid Asmari, Marcos Penedo, Georg Fantner, Ziv Porat, Ido Azuri, Irit Rosenhek-Goldian, Chetan E Chitnis, Yechiel Shai, Neta Regev-Rudzki","doi":"10.1016/j.jbc.2025.108298","DOIUrl":"https://doi.org/10.1016/j.jbc.2025.108298","url":null,"abstract":"Hundreds of thousands die annually from malaria caused by Plasmodium falciparum (Pf), with the emergence of drug-resistant parasites hindering eradication efforts. Antimicrobial peptides (AMPs) are known for their ability to disrupt pathogen membranes without targeting specific receptors, thereby reducing the chance of drug resistance. However, their effectiveness and the biophysical mechanisms by which they target the intracellular parasite remain unexplored. Here, by using native and synthetic AMPs, we discovered a selective mechanism that underlies the anti-malaria activity. Remarkably, the AMPs exclusively interact with Pf-infected Red Blood Cells (Pf-iRBCs), disrupting the cytoskeletal network and reaching the enclosed parasites with correlation to their activity. Moreover, we showed that the unique feature of reduced cholesterol content in the membrane of the infected host makes Pf-iRBCs susceptible to AMPs. Overall, this work highlights the Achilles' heel of malaria parasite and demonstrates the power of AMPs as potential antimalarial drugs with reduced risk of resistance.","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":" ","pages":"108298"},"PeriodicalIF":4.0,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458065","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

Hypoxia induces ferroptotic cell death mediated by activation of the inner mitochondrial membrane fission protein MTP18/Drp1 in invertebrates.

IF 4 2区生物学

Journal of Biological Chemistry Pub Date : 2025-02-17 DOI: 10.1016/j.jbc.2025.108326

Jiaqi Liu, Xichao Sun, Yijie Wu, Zhimin Lv, Na Zhou, Chao Bian, Shengming Sun

{"title":"Hypoxia induces ferroptotic cell death mediated by activation of the inner mitochondrial membrane fission protein MTP18/Drp1 in invertebrates.","authors":"Jiaqi Liu, Xichao Sun, Yijie Wu, Zhimin Lv, Na Zhou, Chao Bian, Shengming Sun","doi":"10.1016/j.jbc.2025.108326","DOIUrl":"https://doi.org/10.1016/j.jbc.2025.108326","url":null,"abstract":"Hypoxia and ischemia damage sensitive organelles such as mitochondria, thus mitochondrial dysfunction contributes to metabolic disorders in crustaceans under hypoxia. The mechanisms associated with ferroptosis in hypoxic disorders have not been determined in crustaceans. In particular, the early molecular events of mitochondrial dynamics in crustaceans require clarification. In this study, two evolutionarily conserved mitochondrial fission proteins, Drp1 and MTP18, were identified in the oriental river prawn (Macrobrachium nipponense). In vitro, ferroptosis-mediated impairment of mitochondrial membrane potential was induced by hypoxia in oriental river prawn hemocytes. In hypoxia-induced hemocytes, activation of Drp1 by increased phosphorylation at S616 was identified. Drp1 mitochondrial translocation also increased, and mitochondrial fusion-related protein expression decreased in vivo. Altered mitochondrial fission-fusion dynamics have been linked to mitochondrial dysfunction, inducing a classic ferroptosis mechanism. Marf overexpression or Drp1 knockdown protected against mitochondrial dysfunction and ferroptotic cell death in vitro. Furthermore, hypoxia-induced mitochondrial fission was verified to be driven by the Drp1/MTP18 interaction. Under hypoxia, MTP18 transcription was increased by the binding of activated HIF-1α to hypoxia response elements (HREs) in its promoter. Conjointly, MTP18 knockdown resulted in less apoptosis and decreased prawn mortality in gill tissue in vitro; suggesting that adaptation to hypoxia involves a vital function of MTP18. In conclusion, we uncovered a conserved role of mitochondrial fission in hypoxia-induced ferroptotic cell death. Therefore, we suggest that specific modulation of MTP18/DRP1-mediated mitochondrial dynamics might be a potential therapeutic strategy in hypoxic stress-induced tissue injury of invertebrates.","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":" ","pages":"108326"},"PeriodicalIF":4.0,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458107","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

Utility of binding protein fusions to immunoglobulin heavy chain constant regions from mammalian and avian species.

IF 4 2区生物学

Journal of Biological Chemistry Pub Date : 2025-02-17 DOI: 10.1016/j.jbc.2025.108324

Ningyu Zhu, Philip M Smallwood, John Williams, Yanshu Wang, Jeremy Nathans

{"title":"Utility of binding protein fusions to immunoglobulin heavy chain constant regions from mammalian and avian species.","authors":"Ningyu Zhu, Philip M Smallwood, John Williams, Yanshu Wang, Jeremy Nathans","doi":"10.1016/j.jbc.2025.108324","DOIUrl":"https://doi.org/10.1016/j.jbc.2025.108324","url":null,"abstract":"Antibodies are of central importance as reagents for the localization of proteins and other biomolecules in cells and tissues. To expand the repertoire of antibody-based reagents, we have constructed a series of plasmid vectors that permit expression of amino-terminal fusions to the hinge and Fc regions from goat, guinea pig, human, mouse, and rabbit IgGs, and chicken IgY. The resulting fusion proteins can be produced in transfected mammalian cells and detected with commercially available and species-specific secondary antibody reagents. We demonstrate the utility of this platform by constructing and testing Fc fusions with DARPin, single chain (sc)Fv, nanobody, toxin, and chemokine partners. The resulting fusion proteins were used to detect their targets in tissue sections or on the surface of transfected cells by immunofluorescent staining, or on the surface of immune cells by flow cytometry. By expanding the range of Fc sequences available for fusion protein production, this platform will expand the repertoire of primary antibody reagents for multiplexed immunostaining and FACS analyses.","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":" ","pages":"108324"},"PeriodicalIF":4.0,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458109","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

eIF3d and eIF4G2 mediate an alternative mechanism of cap-dependent but eIF4E-independent translation initiation.

IF 4 2区生物学

Journal of Biological Chemistry Pub Date : 2025-02-17 DOI: 10.1016/j.jbc.2025.108317

Jacob N K Quartey, Dixie J Goss

{"title":"eIF3d and eIF4G2 mediate an alternative mechanism of cap-dependent but eIF4E-independent translation initiation.","authors":"Jacob N K Quartey, Dixie J Goss","doi":"10.1016/j.jbc.2025.108317","DOIUrl":"https://doi.org/10.1016/j.jbc.2025.108317","url":null,"abstract":"Initiation of translation for the majority of eukaryotic mRNAs is mediated by a 5' cap structure to which the eukaryotic Initiation Factor 4E (eIF4E) binds. Inhibition of the activity of eIF4E by 4EBP-1 does not prevent the translation of a number of cellular capped mRNAs, indicative of the existence of previously unexplored mechanisms for the translation of these capped mRNAs without the requirement of eIF4E. eIF4G2, also known as Death Associated Protein 5 (DAP5), a homolog of eIFGI that lacks the eIF4E binding domain, utilizes eIF3d (a subunit of eIF3) to promote the translation of a subset of these mRNAs. Using fluorescence anisotropy-based equilibrium binding studies, we provide the first quantitative evidence of the recruitment of eIF3d as well as eIF3d and eIFG2 complexes to a subset of human mRNAs. Our quantitative studies demonstrate the critical role a fully methylated 5' mRNA cap structure plays in the recognition and recruitment of eIF3d, as well as the eIF3d and eIFG2 complex. By using luciferase reporter-based in vitro translation assays, we further show that cap-recognition ability correlates with the efficiency of translation of these mRNAs. Essentially, by preferably utilizing eIF3d and eIFG2, specific mRNA subsets are still able to translate in a cap-dependent manner even when eIF4E is sequestered. Our findings offer new insight into the use of eIF3d and eIF4G2 as an alternative for growth and survival under conditions of cellular stress. This novel mechanism of translation may offer new targets for therapeutic regulation of mRNA translation.","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":" ","pages":"108317"},"PeriodicalIF":4.0,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458088","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

Withdrawal: RNA Silencing Identifies PDE4D5 as the Functionally Relevant cAMP Phosphodiesterase Interacting with βArrestin to Control the Protein Kinase A/AKAP79-mediated Switching of the β₂-Adrenergic Receptor to Activation of ERK in HEK293B2 Cells.

IF 4 2区生物学

Journal of Biological Chemistry Pub Date : 2025-02-16 DOI: 10.1016/j.jbc.2024.108141

Martin J Lynch, George S Baillie, Ahmed Mohamed, Xiang Li, Charlotte Maisonneuve, Enno Klussmann, Gino van Heeke, Miles D Houslay

引用次数: 0

Correction: A putative cAMP-binding protein in Trypanosoma brucei cooperates with FLAM3 to promote flagellar connection and cell morphogenesis.

IF 4 2区生物学

Journal of Biological Chemistry Pub Date : 2025-02-15 DOI: 10.1016/j.jbc.2025.108238

Qing Zhou, Phu Van Nguyen, Ziyin Li

引用次数: 0

Isolation and structure elucidation of Dm-CVNH, a new cyanovirin-N homolog with activity against SARS-CoV-2 and HIV-1.

IF 4 2区生物学

Journal of Biological Chemistry Pub Date : 2025-02-14 DOI: 10.1016/j.jbc.2025.108319

Maria Orfanoudaki, Lauren R H Krumpe, Shilpa R Shenoy, Jennifer Wilson, Tad Guszczynski, Curtis J Henrich, J Sebastian Temme, Jeffrey C Gildersleeve, Elisa Molina-Molina, Itziar Erkizia, Julià Blanco, Nuria Izquierdo-Useros, Fabio Montiero, Amilcar Tanuri, Elibio Rech, Barry R O'Keefe

{"title":"Isolation and structure elucidation of Dm-CVNH, a new cyanovirin-N homolog with activity against SARS-CoV-2 and HIV-1.","authors":"Maria Orfanoudaki, Lauren R H Krumpe, Shilpa R Shenoy, Jennifer Wilson, Tad Guszczynski, Curtis J Henrich, J Sebastian Temme, Jeffrey C Gildersleeve, Elisa Molina-Molina, Itziar Erkizia, Julià Blanco, Nuria Izquierdo-Useros, Fabio Montiero, Amilcar Tanuri, Elibio Rech, Barry R O'Keefe","doi":"10.1016/j.jbc.2025.108319","DOIUrl":"https://doi.org/10.1016/j.jbc.2025.108319","url":null,"abstract":"An anti-HIV screening of natural product extracts resulted in the discovery of a new antiviral protein through bioassay-guided fractionation of an aqueous extract of the ascidian Didemnum molle. The protein was sequenced through a combination of tandem mass spectroscopy and N-terminal Edman degradation of peptide fragments after a series of endoproteinase digestions. The primary amino acid sequence and disulfide bonding pattern of the 102-amino acid protein were closely related to the antiviral protein cyanovirin-N (CV-N). This new CV-N homolog was named Dm-CVNH. Alphafold2 prediction resulted in a tertiary structure, highly similar to CV-N, comprised of two symmetrically related domains that contained five β-strands and two α-helical turns each. Dm-CVNH showed specificity for high mannose and oligomannose structures, bound to HIV-1 gp-120 and potently inactivated HIV in neutralization assays (EC50 of 0.95 nM). Dm-CVNH inhibited infection in a SARS-CoV-2 live virus assays (EC50 = 11-18 nM) and was shown to bind to the S1 domain of SARS-CoV-2 Spike glycoprotein. Dm-CVNH behaved in a manner similar to CV-N, binding with a 2:1 stoichiometry to Spike (both to WH-1 and Omicron variants) and preferring the Omicron variant (Kd 42 nM) to original WH-1 (Kd = 89 nM) Spike. This sensitivity to emergent strains was mirrored in viral neutralization assays where Dm-CVNH potently inhibited the infection of Omicron strains XBB.1.16 and JN.1 (IC50 = 11-18 nM).","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":" ","pages":"108319"},"PeriodicalIF":4.0,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433224","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

Substrate-specific effects point to the important role of Y361 as part of the YER motif in closing the binding pocket of OCT1.

IF 4 2区生物学

Journal of Biological Chemistry Pub Date : 2025-02-14 DOI: 10.1016/j.jbc.2025.108318

Sarah Römer, Erika Lazzarin, Anna Neumann, Erik Lindemann, Marleen J Meyer-Tönnies, Thomas Stockner, Mladen V Tzvetkov

{"title":"Substrate-specific effects point to the important role of Y361 as part of the YER motif in closing the binding pocket of OCT1.","authors":"Sarah Römer, Erika Lazzarin, Anna Neumann, Erik Lindemann, Marleen J Meyer-Tönnies, Thomas Stockner, Mladen V Tzvetkov","doi":"10.1016/j.jbc.2025.108318","DOIUrl":"https://doi.org/10.1016/j.jbc.2025.108318","url":null,"abstract":"Organic cation transporter 1 (OCT1) is located in the sinusoidal membrane of human hepatocytes. It mediates the uptake of hydrophilic organic cationic drugs in hepatocytes and thus determine their systemic concentrations. OCT1 has a broad spectrum of structurally diverse substrates like metformin, sumatriptan, trospium, and fenoterol. Recent cryo-EM data suggested that Y361, E386, and R439, referred to as the YER motif, could be important for transport. Building on this, we used extensive functional analyses to investigate the general function, and the substrate-specific effects of the YER motif. We determined the activity of the Y361A, E386A, and R439A mutants for fifteen OCT1 substrates. Extended mutagenesis revealed the negative charge of E386 and the positive charge of R439 as essential for the transport of all substrates tested. Charge reversal mutants, E386R-R439E, did not restore transport activity, suggesting that at least one of the two amino acids is involved in additional interactions essential for transport. Y361 exhibited substrate-specific effects. The Y361A mutant transported fenoterol, but not pirbuterol or other beta2-adrenergic drugs with only one aromatic ring. MD simulations suggested that substrates with aromatic or lipophilic characteristics may compensate for the missing aromatic ring at position 361. Only tryptophan at codon 361 efficiently rescued the transport of the Y361A mutant supporting hydrogen bound interaction with E386 and R439. Our study confirms that the YER motif is essential for OCT1 transport and points to Y361 as a lever that interacts with E386 and R439 to trigger the closing of the binding pocket of human OCT1.","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":" ","pages":"108318"},"PeriodicalIF":4.0,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433225","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

Binding of small molecules at the P-stalk site of ricin A subunit trigger conformational changes that extend into the active site.

IF 4 2区生物学

Journal of Biological Chemistry Pub Date : 2025-02-14 DOI: 10.1016/j.jbc.2025.108310

John E McLaughlin, Michael J Rudolph, Arkajyoti Dutta, Xiao-Ping Li, Anastasiia M Tsymbal, Yang Chen, Shibani Bhattacharya, Benjamin Algava, Michael Goger, Jacques Y Roberge, Nilgun E Tumer

{"title":"Binding of small molecules at the P-stalk site of ricin A subunit trigger conformational changes that extend into the active site.","authors":"John E McLaughlin, Michael J Rudolph, Arkajyoti Dutta, Xiao-Ping Li, Anastasiia M Tsymbal, Yang Chen, Shibani Bhattacharya, Benjamin Algava, Michael Goger, Jacques Y Roberge, Nilgun E Tumer","doi":"10.1016/j.jbc.2025.108310","DOIUrl":"10.1016/j.jbc.2025.108310","url":null,"abstract":"Ricin is a category B agent for bioterrorism, and Shiga toxins are the primary virulence factors of Shiga toxin (Stx) producing Escherichia coli. Ricin and Stxs bind the ribosomal P-stalk proteins to depurinate the sarcin/ricin loop on the eukaryotic ribosome and inhibit translation. Both toxins are prime targets for therapeutic intervention because no effective therapy exists for ricin intoxication or Shiga toxin producing Escherichia coli infection. Binding of ricin toxin A subunit (RTA) to the ribosomal P-stalk stimulates depurination of the sarcin/ricin loop by an unknown mechanism. We previously identified compounds that bind the P-stalk pocket of RTA and inhibit catalytic activity. Here we characterize a second-generation lead compound, which binds the P-stalk pocket of RTA with over 30-fold improved affinity relative to the original compound and inhibits the cytotoxicity of ricin holotoxin in Vero cells with no apparent cellular toxicity by itself. This compound also shows protection against Stx2A1. X-ray crystal structure of RTA-inhibitor complexes suggests that the orientation of the carboxylic acid influences the inhibitor contacts at the P-stalk site of RTA and contributes to inhibitor potency. The structural changes triggered at the P-stalk site of RTA were validated by solution NMR-based chemical shift perturbation analysis. A key finding by NMR is that binding-induced conformational changes extend beyond the P-stalk site to residues in the active site cleft of RTA. Collectively, these results provide valuable new insight into the conformational flexibility in the C-terminal domain of RTA and its potential role in mediating the remarkable catalytic activity of ricin.","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":" ","pages":"108310"},"PeriodicalIF":4.0,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425366","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

Sulfoglycolysis sustains Eubacterium rectale in low-fiber diets.

IF 4 2区生物学

Journal of Biological Chemistry Pub Date : 2025-02-14 DOI: 10.1016/j.jbc.2025.108320

Mahima Sharma, Nicholas Pudlo, Michael A Järvå, Arashdeep Kaur, Alan John, Laura Burchill, James P Lingford, Ruwan Epa, Palika Abayakoon, Nichollas E Scott, Johan P Turkenburg, Gideon J Davies, Eric C Martens, Ethan D Goddard-Borger, Spencer J Williams

{"title":"Sulfoglycolysis sustains Eubacterium rectale in low-fiber diets.","authors":"Mahima Sharma, Nicholas Pudlo, Michael A Järvå, Arashdeep Kaur, Alan John, Laura Burchill, James P Lingford, Ruwan Epa, Palika Abayakoon, Nichollas E Scott, Johan P Turkenburg, Gideon J Davies, Eric C Martens, Ethan D Goddard-Borger, Spencer J Williams","doi":"10.1016/j.jbc.2025.108320","DOIUrl":"https://doi.org/10.1016/j.jbc.2025.108320","url":null,"abstract":"The production of short-chain fatty acids (SCFAs) by Firmicutes (Bacillota) within the human gastrointestinal tract is recognized as critical for gut health and the progression of a range of disease states. Firmicutes are the most diverse phylum of human gut bacteria and are highly studied, and are often specialized to degrade just a few polysaccharide substrates. Members of the Firmicutes include key bacteria that produce butyrate, an SCFA that is generally not produced by members of the other major phyla. Recently, it was shown that Eubacterium rectale, a widespread member of the Firmicutes belonging to the Clostridiales cluster XIVa, can grow on the unusual but ubiquitous plant-derived sugar SQ using a sulfoglycolytic sulfofructose transaldolase pathway. Here, we show that in addition to SQ, E. rectale can also grow on the SQ glycoside sulfoquinovosyl glycerol (SQGro). The 3D structure of the E. rectale sulfoquinovosidase (SftG) shares strong structural conservation with other carbohydrate active enzyme family GH31 SQases. Using sequence-similarity networks, we provide new biological context to a conserved domain of unknown function protein SftX belonging to DUF4867, which is conserved in the sulfoglycolytic sulfofructose transaldolase pathway, and determine its 3D structure. Finally, with the aid of a synthetic mini-human microbiome reconstituted in germ-free mice, we show that an SQ dietary supplement can rescue E. rectale from population crashes that occur upon switching from a high-fiber to a low-fiber, high-fat diet. This suggests that SQ or SQGro has potential as a prebiotic for promoting the maintenance of this important butyrate-producing bacterium within the colonic microbiota.","PeriodicalId":15140,"journal":{"name":"Journal of Biological Chemistry","volume":" ","pages":"108320"},"PeriodicalIF":4.0,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433226","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