Interferon gamma-inducible protein 16(IFI16)senses DNA in the cytoplasm and the nucleus by using two tandem hematopoietic interferon-inducible nuclear(HIN)domains,HINa and HINb,through the cooperative assembly of IFI1...Interferon gamma-inducible protein 16(IFI16)senses DNA in the cytoplasm and the nucleus by using two tandem hematopoietic interferon-inducible nuclear(HIN)domains,HINa and HINb,through the cooperative assembly of IFI16 filaments on double-stranded DNA(dsDNA).The role of HINa in sensing DNA is not clearly understood.Here,we describe the crystal structure of the HINa domain in complex with DNA at 2.55A°resolution and provide the first insight into the mode of DNA binding by the HINa domain.The structure reveals the presence of two oligosaccharide/nucleotide-binding(OB)folds with a unique DNA-binding surface.HINa uses loop L45 of the canonical OB2 fold to bind to the DNA backbone.The dsDNA is recognized as two single strands of DNA.Interestingly,deletion of HINb compromises the ability of IFI16 to induce IFN-b,while HINa mutants impaired in DNAbinding enhance the production of IFN-b.These results shed light on the roles of IFI16 HIN domains in DNA recognition and innate immune responses.展开更多
Gluten,known as the major allergen in wheat,has gained increasing concerns in industrialized countries,resulting in an urgent need for accurate,high-sensitive,and on-site detection of wheat gluten in complex food syst...Gluten,known as the major allergen in wheat,has gained increasing concerns in industrialized countries,resulting in an urgent need for accurate,high-sensitive,and on-site detection of wheat gluten in complex food systems.Herein,we proposed a silver nanoparticles(AgNPs)/metal-organic framework(MOF)substrate-based surface-enhanced Raman scattering(SERS)sensor for the high-sensitive on-site detection of wheat gluten.The detection occurred on the newly in-situ synthesized AgNPs/MOF-modified SERS substrate,providing an enhancement factor(EF)of 1.89×10^(5).Benefitting from the signal amplification function of AgNPs/MOF and the superiority of SERS,this sensor represented high sensitivity performance and a wide detection range from 1×10^(-15)mol/L to 2×10^(-6)mol/L with a detection limit of 1.16×10^(-16)mol/L,which allowed monitoring the trace of wheat gluten in complex food system without matrix interference.This reliable sandwich SERS sensor may provide a promising platform for high-sensitive,accurate,and on-site detection of allergens in the field of food safety.展开更多
Recognition of CpG dinucleotide DNA in epigenetic information flow plays a pivotal role for cellular differentiation and development.The TET3 CXXC domain binds to CpG DNA,serving a basic epigenetic information reading...Recognition of CpG dinucleotide DNA in epigenetic information flow plays a pivotal role for cellular differentiation and development.The TET3 CXXC domain binds to CpG DNA,serving a basic epigenetic information reading mechanism.During the selective recognition of a CpG motif by a CXXC domain from crowded binding sites in a gene sequence,the protein-DNA interactions are beyond CpG dinu-cleotide.However,the selective binding dynamics of CpG within a long DNA context by epigenetic enzymes have been rarely exploit-ed,which is hard for ensemble methods to probe.Here,we used single-molecule magnetic tweezers to quantitatively examine the dynamics of TET3's CXXC domain on a Hoxa9 promoter DNA.Our single-molecule binding profile revealed that CXXC-DNA interactions involve both CpG motifs and their flanking sequences.The residence time of TET3 CXXC differs by about 1000 times in five distin-guished CpG clusters in the context of a CpG island.Moreover,we performed multi-state hidden Markov modeling analysis on the zip-ping/unzipping dynamics of a CpG hairpin,discovering TET3 CXXC's preference on CpG motifs regarding the-2 to+2 flanking bases.Our results shed light on the selective binding dynamics of a CXXC on a gene sequence,facilitating studies on epigenetic information reading mechanisms.展开更多
基金supported by the National Natural Science Foundation of China(grant no.31570875,31330019,31200559,and 81590761)the Ministry of Science and Technology of China(grant no.2014CB910400 and 2013CB911103)+2 种基金the National Science and Technology Major Project of China(grant no.2013ZX10004-602)the Beijing Nova Program(grant no.Z141102001814020)Youth Innovation Promotion Association CAS,and the special project of Ebola virus research from the president foundation of Chinese Academy of Sciences.
文摘Interferon gamma-inducible protein 16(IFI16)senses DNA in the cytoplasm and the nucleus by using two tandem hematopoietic interferon-inducible nuclear(HIN)domains,HINa and HINb,through the cooperative assembly of IFI16 filaments on double-stranded DNA(dsDNA).The role of HINa in sensing DNA is not clearly understood.Here,we describe the crystal structure of the HINa domain in complex with DNA at 2.55A°resolution and provide the first insight into the mode of DNA binding by the HINa domain.The structure reveals the presence of two oligosaccharide/nucleotide-binding(OB)folds with a unique DNA-binding surface.HINa uses loop L45 of the canonical OB2 fold to bind to the DNA backbone.The dsDNA is recognized as two single strands of DNA.Interestingly,deletion of HINb compromises the ability of IFI16 to induce IFN-b,while HINa mutants impaired in DNAbinding enhance the production of IFN-b.These results shed light on the roles of IFI16 HIN domains in DNA recognition and innate immune responses.
基金financially supported by the Zhejiang Provincial Natural Science Foundation of China(LY21C200008)。
文摘Gluten,known as the major allergen in wheat,has gained increasing concerns in industrialized countries,resulting in an urgent need for accurate,high-sensitive,and on-site detection of wheat gluten in complex food systems.Herein,we proposed a silver nanoparticles(AgNPs)/metal-organic framework(MOF)substrate-based surface-enhanced Raman scattering(SERS)sensor for the high-sensitive on-site detection of wheat gluten.The detection occurred on the newly in-situ synthesized AgNPs/MOF-modified SERS substrate,providing an enhancement factor(EF)of 1.89×10^(5).Benefitting from the signal amplification function of AgNPs/MOF and the superiority of SERS,this sensor represented high sensitivity performance and a wide detection range from 1×10^(-15)mol/L to 2×10^(-6)mol/L with a detection limit of 1.16×10^(-16)mol/L,which allowed monitoring the trace of wheat gluten in complex food system without matrix interference.This reliable sandwich SERS sensor may provide a promising platform for high-sensitive,accurate,and on-site detection of allergens in the field of food safety.
基金Professor Chao Xu of the University of Science and Technology of China(UsTC)for constructive discussions.We acknowledge support from the National Natural Science Foundation of China[Grant 32071227 to Z.Y.]State Key Laboratory of Precision Measuring Technology and Instruments(Tianjin University)[Grant pilab2210 to Z.Y.]+1 种基金the Natural Science Foundation of Tianjin[Grant 22JCYBJC01070 to Z.Y.]the Science and Technology Innovation Program of Shanxi Agricultural University[Grant 2022BQ23 to L.L.].
文摘Recognition of CpG dinucleotide DNA in epigenetic information flow plays a pivotal role for cellular differentiation and development.The TET3 CXXC domain binds to CpG DNA,serving a basic epigenetic information reading mechanism.During the selective recognition of a CpG motif by a CXXC domain from crowded binding sites in a gene sequence,the protein-DNA interactions are beyond CpG dinu-cleotide.However,the selective binding dynamics of CpG within a long DNA context by epigenetic enzymes have been rarely exploit-ed,which is hard for ensemble methods to probe.Here,we used single-molecule magnetic tweezers to quantitatively examine the dynamics of TET3's CXXC domain on a Hoxa9 promoter DNA.Our single-molecule binding profile revealed that CXXC-DNA interactions involve both CpG motifs and their flanking sequences.The residence time of TET3 CXXC differs by about 1000 times in five distin-guished CpG clusters in the context of a CpG island.Moreover,we performed multi-state hidden Markov modeling analysis on the zip-ping/unzipping dynamics of a CpG hairpin,discovering TET3 CXXC's preference on CpG motifs regarding the-2 to+2 flanking bases.Our results shed light on the selective binding dynamics of a CXXC on a gene sequence,facilitating studies on epigenetic information reading mechanisms.