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Spike N354 glycosylation augments SARS-CoV-2 fitness for human adaptation through structural plasticity

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National Science Review 2024年第7期11卷 80-94页

作者： Pan Liu Can Yue Bo Meng Tianhe Xiao Sijie Yang Shuo Liu Fanchong Jian Qianhui Zhu Yuanling Yu Yanyan Ren Peng Wang Yixin Li Jinyue Wang Xin Mao Fei Shao Youchun Wang Ravindra Kumar Gupta Yunlong Cao Xiangxi Wang CAS Key laboratory of Infection and Immunity National Laboratory of MacromoleculesInstitute of BiophysicsChinese Academy of Sciences University of Chinese Academy of Sciences Cambridge Institute of Therapeutic Immunology&Infectious Disease(CITIID) University of Cambridge Biomedical Pioneering innovation Center(BIOPIC) Peking University Changping laboratory Joint Graduate Program of Peking-Tsinghua-NIBS Academy for Advanced Interdisciplinary Studies Peking University Peking-Tsinghua Center for Life Sciences Tsinghua University Chinese Academy of Medical Sciences&Peking Union Medical College

Selective pressures have given rise to a number of SARS-CoV-2 variants during the prolonged course of the COVID-19 pandemic. Recently evolved variants differ from ancestors in additional glycosylation within the spike protein receptor-binding domain(RBD). Details of how the acquisition of glycosylation impacts viral fitness and human adaptation are not clearly understood. Here, we dissected the role of N354-linked glycosylation, acquired by BA.2.86 sub-lineages, as a RBD conformational control element in attenuating viral infectivity. The reduced infectivity is recovered in the presence of heparin sulfate, which targets the‘N354 pocket’ to ease restrictions of conformational transition resulting in a ‘RBD-up’ state, thereby conferring an adjustable infectivity. Furthermore, N354 glycosylation improved spike cleavage and cell–cell fusion, and in particular escaped one subset of ADCC antibodies. Together with reduced immunogenicity in hybrid immunity background, these indicate a single spike amino acid glycosylation event provides selective advantage in humans through multiple mechanisms.

关键词： coronavirus glycosylation viral fitness adjustable infectivity co-factor usage viral evolution conformational modulator

AP-3 adaptor complex-mediated vesicle trafficking

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biophysics Reports 2021年第2期7卷 91-100页

作者： Zhuo Ma Md.Nur Islam Tao Xu Eli Song National laboratory of Biomacromolecules CAS Center for Excellence in Biomacromolecules Institute of Biophysics Chinese Academy of Sciences University of Chinese Academy of Sciences Guangzhou Regenerative Medicine and Health Guangdong laboratory(Bioland laboratory)

The transport of cargo proteins to specific subcellular destinations is crucial for the different secretory and endocytic traffic pathways. One of the most important steps in maintaining the accuracy of this process is the recruitment of adaptor protein(AP) complexes to the membrane for recognizing and packaging cargo proteins into nascent vesicles. Adaptor protein complex 3(AP-3) is a heterotetrametric complex implicated in the trafficking of cargo proteins from the trans-Golgi network(TGN) and/or endosomes to lysosomes or lysosome-related organelles(LROs). This complex is also involved in the biogenesis of synaptic vesicles(SVs) in neurons and of dense core vesicles(DCVs) in endocrine cells as well as in the recycling of receptors in immune cells and the regulation of planar cell polarity(PCP)proteins. Functional defects in AP-3 cause multiple abnormalities in cellular vesicle trafficking and related organelle function, leading to various disorders, such as Hermansky-Pudlak syndrome(HPS).However, the molecular mechanism underlying AP-3 has not been fully elucidated, and further investigations are needed to understand AP-3-mediated trafficking, its associated molecules and its related roles in inherited diseases. Here, we review the current understanding of AP-3 in cellular vesicle trafficking, especially focusing on mammalian systems.

关键词： AP-3 Vesicle trafficking Cargo sorting Disease/disorder

The Fast Track for Microbiome Research

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Genomics, Proteomics & Bioinformatics 2019年第1期17卷 1-3页

作者： Kang Ning Yigang Tong MOE Key laboratory of Molecular biophysics Hubei Key Laboratory of Bioinformatics and Molecular-imaging Department of Bioinformatics and Systems Biology College of Life Science and Technology Huazhong University of Science and Technology College of Life Science and Technology Beijing University of Chemical Technology Beijing Advanced innovation Center for Soft Matter Science and Engineering (BAIC-SM) Beijing University of Chemical Technology

The microbiome research is undoubtedly one of the most popular topics in biomedical research *** is not without reason:given that microbiome is found to be linked with and sometime causes chronic diseases and even cancers,it has become more and more obvious that microbiome plays crucial roles in human health and the surrounding environments.

关键词： microbiome research most popular surrounding environments

Bioinformatics Commons: The Cornerstone of Life and Health Sciences

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Genomics,Proteomics & Bioinformatics 2018年第4期16卷 223-225页

作者： Zhang Zhang Yu Xue Fangqing Zhao BIG Data Center and CAS Key laboratory of Genome Sciences & Information Beijing Institute of Genomics Chinese Academy of Sciences Department of Bioinformatics & Systems Biology MOE Key Laboratory of Molecular Biophysics College of Life Science and Technology and the Collaborative Innovation Center for Biomedical Engineering Huazhong University of Science and Technology Beijing Institutes of Life Science Chinese Academy of Sciences

Bioinformatics, an interdisciplinary field that combines biology, mathematics, computer science, medicine, and health science, to integrate, analyze, and interpret biological data, is now becoming increasingly data-intensive. To dig out the treasure from big data powered by high-throughput sequencing technologies, it is highly dependent on Bioinformatics Commons that involves a variety of fundamental resources, includ-

关键词： Bioinformatics Commons The Cornerstone of Life and Health Sciences

Junctional and somatic hypermutation-induced CX4C motif is critical for the recognition of a highly conserved epitope on HCV E2 by a human broadly neutralizing antibody

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Cellular & Molecular Immunology 2021年第3期18卷 675-685页

作者： Chunyan Yi Jing Xia Lan He Zhiyang Ling Xuesong Wang Yu Yan Jiangjun Wang Xinhao Zhao Weiguo Fan Xiaoyu Sun Ronghua Zhang Sheng Ye Rongguang Zhang Yongfen Xu Liyan Ma Yaguang Zhang Honglin Zhou Zhong Huang Junqi Niu Gang Long Junxia Lu Jin Zhong Bing Sun State Key laboratory of Cell Biology CAS Center for Excellence in Molecular Cell ScienceShanghai Institute of Biochemistry and Cell BiologyChinese Academy of Sciences/University of Chinese Academy of SciencesShanghaiChina CAS Key laboratory of Molecular Virology and Immunology Institut Pasteur of ShanghaiChinese Academy of Sciences/University of Chinese Academy of SciencesShanghaiChina School of Life Science and Technology ShanghaiTech UniversityShanghaiChina CAS Key laboratory of Synthetic Chemistry of Natural Substances Shanghai Institute of Organic ChemistryChinese Academy of SciencesShanghaiChina College of Biology Hunan Provincial Key Laboratory of Medical VirologyHunan UniversityChangshaChina National laboratory of biophysics Institute of BiophysicsChinese Academy of Sciences/University of Chinese Academy of Sciences BdjingBeijingChina Interdisciplinary innovation Institute of Medicine&Engineering Beijing Advanced Innovation Center for Big Data-Based Precision MedicineSchool of Biological Science and Medical EngineeringBeihang UniversityBeijingChina Nanjing Galaxy Biopharma Co. LtdNanjingChina Hepatology Section First HospitalUniversity of JilinChangchunChina

Induction of broadly neutralizing monoclonal antibodies(bNAbs)that bind to the viral envelope glycoproteins is a major goal of hepatitis C virus(HCV)vaccine *** study of bNAbs arising in natural infection is essential in this *** generated a human antibody,8D6,recognizing the E2 protein of HCV isolated from a chronic hepatitis C *** antibody shows broadly neutralizing activity,which covers a pan-genotypic panel of cell culture-derived HCV virions(HCVcc).Functional and epitope analyses demonstrated that 8D6 can block the interaction between E2 and CD81 by targeting a highly conserved epitope on *** describe how the 8D6 lineage evolved via somatic hypermutation to achieve broad *** found that the V(D)J recombination-generated junctional and somatic hypermutation-induced disulfide bridge(C-C)motif in the CDRH3 is critical for the broad neutralization and binding activity of *** motif is conserved among a series of broadly neutralizing HCV antibodies,indicating a common binding ***,the 8D6 inferred germline(iGL)was reconstructed and tested for its binding affinity and neutralization ***,8D6 iGL-mediated relatively strong inhibition of the 1b genotype PR79L9 strain,suggesting that PR79L9 may serve as a potential natural viral strain that provides E2 sequences that induce ***,our detailed epitope mapping and genetic studies of the HCV E2-specific mAb 8D6 have allowed for further refinement of antigenic sites on E2 and reveal a new mechanism to generate a functional CDRH3,while its iGL can serve as a probe to identify potential HCV vaccine strains.

关键词： Hepatitis C virus neutralizing antibody inferred germline CDRH3 disulfide bridge motif

Time-restricted feeding is an intervention against excessive dark-phase sleepiness induced by obesogenic diet

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National Science Review 2023年第1期10卷 127-142页

作者： Xu Wang Keke Xing Mengge He Ting He Xinkuan Xiang Tao Chen Luoying Zhang Haohong Li Britton Chance Center for Biomedical Photonics Wuhan National Laboratory for OptoelectronicsHuazhong University of Science and Technology MOE Key laboratory for Biomedical Photonics Collaborative Innovation Center for Biomedical Engineering School of Engineering SciencesHuazhong University of Science and Technology Department of Anatomy Histology &Embryology Fourth Military Medical University Key laboratory of Molecular biophysics of Ministry of Education College of Life Science and Technology Huazhong University of Science and Technology Department of Neurobiology Affiliated Mental Health Center &Hangzhou Seventh People's HospitalZhejiang University School of Medicine Liangzhu laboratory The MOE Frontier Research Center of Brain &Brain-machine Integration State Key Laboratory of Brain-machine Intelligence

High-fat diet(HFD)-induced obesity is a growing epidemic and major health *** excessive daytime sleepiness(EDS) is a common symptom of HFD-induced obesity,preliminary findings suggest that reduced wakefulness could be improved with time-restricted feeding(TRF).At present,however,the underlying neural mechanisms remain largely *** paraventricular thalamic nucleus(PVT) plays a role in maintaining *** found that chronic HFD impaired the activity of PVT ***,inactivation of the PVT was sufficient to reduce and fragment wakefulness during the active phase in lean mice,similar to the sleep-wake alterations observed in obese mice with HFD-induced *** the other hand,enhancing PVT neuronal activity cons olidated wakefulness in mice with HFD-induced *** observed that the fragmented wakefulness could be eliminated and reversed by ***,TRF prevented the HFD-induced disruptions on synaptic transmission in the PVT,in a feeding duration-dependent ***,our findings demonstrate that ad libitum access to a HFD results in inactivation of the PVT,which is critical to impaired nocturnal wakefulness and increased sleep,while TRF can prevent and reverse diet-induced PVT dysfunction and excessive *** establish a link between TRF and neural activity,through which TRF can potentially serve as a lifestyle intervention against diet/obesity-related ED S.

关键词： high-fat diet excessive daytime sleepiness sleep–wake cycle fragmented wakefulness paraventricular thalamic nucleus time-restricted feeding

Taurine Transporter dEAAT2 is Required for Auditory Transduction in Drosophila

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Neuroscience Bulletin 2018年第6期34卷 939-950页

作者： Ying Sun Yanyan Jia Yifeng Guo Fangyi Chen Zhiqiang Yan State Key laboratory of Medical Neurobiology Human Phenome InstituteMinistry of Education Key Laboratory of Contemporary AnthropologyCollaborative Innovation Center of Genetics and DevelopmentDepartment of Physiology and BiophysicsSchool of Life SciencesFudan UniversityShanghai 200438China Department of Human Anatomy School of Basic Medicine SciencesSouthwest Medical UniversityLuzhou 646000China Department of Biomedical Engineering Southern University of Science and TechnologyShenzhen 518055China

Drosophila dEAAT2, a member of the excitatory amino-acid transporter(EAAT) family, has been described as mediating the high-affinity transport of taurine, which is a free amino-acid abundant in both insects and mammals. However, the role of taurine and its transporter in hearing is not clear. Here, we report that dEAAT2 is required for the larval startle response to sound stimuli. d EAAT2 was found to be enriched in the distal region of chordotonal neurons where sound transduction occurs. The Ca2+imaging and electrophysiological results showed that disrupted dEAAT2 expression significantly reduced the response of chordotonal neurons to *** importantly, expressing d EAAT2 in the chordotonal neurons rescued these mutant phenotypes. Taken together,these findings indicate a critical role for Drosophila dEAAT2 in sound transduction by chordotonal neurons.

关键词： Drosophila dEAAT2 Taurine Chordotonal neurons Sound transduction

SnoRNP is essential for thermospermine-mediated development in Arabidopsis thaliana

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Science China(Life Sciences) 2023年第1期66卷 2-11页

作者： Xilong Li Zongyun Yan Meiling Zhang Jiayin Wang Peiyong Xin Shujing Cheng Liquan Kou Xiaoting Zhang Songlin Wu Jinfang Chu Chengqi Yi Keqiong Ye Bing Wang Jiayang Li State Key laboratory of Plant Genomics and National Center for Plant Gene Research(Beijing) Institute of Genetics and Developmental BiologyInnovation Academy for Seed DesignChinese Academy of SciencesBeijing 100101China State Key laboratory of Protein and Plant Gene Research School of Life SciencesPeking UniversityBeijing 100871China Key laboratory of RNA Biology CAS Center for Excellence in BiomacromoleculesInstitute of BiophysicsChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100039China Hainan Yazhou Bay Seed laboratory Sanya 572025China

Polyamines have been discovered for hundreds of years and once considered as a class of *** play critical roles in a range of developmental ***,the molecular mechanisms of polyamine signaling pathways remain poorly ***,we measured the contents of main types of polyamines,and found that endogenous level of thermospermine(T-Spm)in Arabidopsis thaliana is comparable to those of classic phytohormones and is significantly lower than those of putrescine(Put),spermidine(Spd),and spermine(Spm).We further found a nodule-like structure around the junction area connecting the shoot and root of the T-Spm biosynthetic mutant acl5 and obtained more than 50 suppressors of acl5 nodule structure(san)through suppressor *** in-depth study of two san suppressors revealed that NAP57 and NOP56,core components of box H/ACA and C/D snoRNPs,were essential for T-Spm-mediated nodule-like structure formation and plant ***,analyses of rRNA modifications showed that the overall levels of pseudouridylation and 2′-O-methylation were compromised in san1 and san2 *** together,these results establish a strong genetic relationship between rRNA modification and T-Spm-mediated growth and development,which was previously undiscovered in all organisms.

关键词： polyamines thermospermine snoRNP pseudouridylation 2’-O-methylation Arabidopsis thaliana

Selection for Cheaper Amino Acids Drives Nucleotide Usage at the Start of Translation in Eukaryotic Genes

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Genomics, Proteomics & Bioinformatics 2021年第6期19卷 949-957页

作者： Na L.Gao Zilong He Qianhui Zhu Puzi Jiang Songnian Hu Wei-Hua Chen Key laboratory of Molecular biophysics of the Ministry of Education Hubei Key Laboratory of Bioinformatics and Molecular-imagingDepartment of Bioinformatics and Systems BiologyCollege of Life Science and TechnologyHuazhong University of Science and TechnologyWuhan 430074China Institute for Computer Science and Cluster of Excellence on Plant Sciences Heinrich Heine UniversityD-40225 DuesseldorfGermany CAS Key laboratory of Genome Sciences and Information Beijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China State Key laboratory of Microbial Resources Institute of MicrobiologyChinese Academy of SciencesBeijing 100101China Beijing Advanced innovation Center for Big Data-Based Precision Medicine Interdisciplinary Innovation Institute of Medicine and EngineeringBeihang UniversityBeijing 100191China University of Chinese Academy of Sciences Beijing 100049China

Coding regions have complex interactions among multiple selective forces,which are manifested as biases in nucleotide *** studies have revealed a decreasing GC gradient from the 5′-end to 3′-end of coding regions in various *** confirmed that this gradient is universal in eukaryotic genes,but the decrease only starts from the~25th *** trend is mostly found in nonsynonymous(ns)sites at which the GC gradient is universal across the eukaryotic *** GC contents at ns sites result in cheaper amino acids,indicating a universal selection for energy efficiency toward the N-termini of encoded *** a genome,the decreasing GC gradient is intensified from lowly to highly expressed genes(more and more protein products),further supporting this *** reveals a conserved selective constraint for cheaper amino acids at the translation start that drives the increased GC contents at ns *** GC contents can facilitate transcription but result in a more stable local secondary structure around the start codon and subsequently impede translation ***,the GC gradients at four-fold and two-fold synonymous sites vary across *** could decrease or increase,suggesting different constraints acting at the GC contents of different codon sites in different *** study reveals that the overall GC contents at the translation start are consequences of complex interactions among several major biological processes that shape the nucleotide sequences,especially efficient energy usage.

关键词： Macroevolution Prioritization of selective forces Energy efficiency Transcription Translation initiation