2024年1月3日,浙江大学生命科学研究院陆华松研究员与杨兵研究员团队合作在《自然·细胞生物学》(Nature Cell Biology)发表题为“A chaperone-like function of FUS ensures TAZ condensate dynamics and transcriptional activat...2024年1月3日,浙江大学生命科学研究院陆华松研究员与杨兵研究员团队合作在《自然·细胞生物学》(Nature Cell Biology)发表题为“A chaperone-like function of FUS ensures TAZ condensate dynamics and transcriptional activation”的研究论文(DOI:10.1038/s41556-023-01309-3),揭示了生物大分子凝聚体物质属性与其功能维持的紧密联系,发现FUS具有“分子伴侣样”的新功能,能够维持TAZ凝聚体的流动性,从而促进其转录活性的重要功能。展开更多
SIRT1(Sirtuin type 1)作为Sirtuins家族最重要的成员之一,具有去乙酰化酶活性,不仅参与代谢、能量感应途径、昼夜节律机制和炎症等过程,而且作为一种表观遗传修饰物,影响DNA的损伤修复及染色体的稳定。除了参与体内众多基因转录及能量...SIRT1(Sirtuin type 1)作为Sirtuins家族最重要的成员之一,具有去乙酰化酶活性,不仅参与代谢、能量感应途径、昼夜节律机制和炎症等过程,而且作为一种表观遗传修饰物,影响DNA的损伤修复及染色体的稳定。除了参与体内众多基因转录及能量代谢外,SIRT1还可以调节细胞的衰老过程,改善或延缓与年龄相关的疾病进程。SIRT1基因多态性可作为治疗不同疾病的靶点,与多种人类相关疾病的发病机制有关,本文将对SIRT1基因多态性与相关疾病的关系作一综述。展开更多
深度学习方法已经彻底改变了蛋白质结构预测和设计,但目前仅限于蛋白质系统。研究人员描述了RoseT‐TAFold All Atom(RFAA),它可以将氨基酸和DNA碱基的基于残基的表示符号与所有其他基团的原子表示符号相结合,从而对给定序列和化学结构...深度学习方法已经彻底改变了蛋白质结构预测和设计,但目前仅限于蛋白质系统。研究人员描述了RoseT‐TAFold All Atom(RFAA),它可以将氨基酸和DNA碱基的基于残基的表示符号与所有其他基团的原子表示符号相结合,从而对给定序列和化学结构的包含蛋白质、核酸、小分子、金属和共价修饰的组件进行建模。通过对去噪任务进行微调,科学家们获得了RFdiffusionAA,它能围绕小分子构建蛋白质结构。从围绕目标小分子的氨基酸残基的随机分布开始,研究人员通过晶体学和结合测量学,设计并实验验证了与心脏病治疗药物地高辛、酶促辅因子血红素和光捕获分子bilin结合的蛋白质。展开更多
Life requires more than nucleic acids and proteins;sweet sugar molec ules could be ano ther life code beyond the central dogma of molecular biology.There are four equally important major building blocks of life:nuclei...Life requires more than nucleic acids and proteins;sweet sugar molec ules could be ano ther life code beyond the central dogma of molecular biology.There are four equally important major building blocks of life:nucleic acids(DNA and RNA),proteins,carbohydrates(glycans),and lipids.The first two are also known as the first and second alphabets of biology,following the principle of the"central dogma"of transcription(DNA to RNA)and trahslation(RNA to protein).However,the latter two crucial components,glycans and lipids,are missing from biology's central dogma Regarding the communi-cation between glycans and lipids,there may be a yet-to-be-discovered law:Does a paracentral dogma exist?This commentary focuses on glycans,the third alphabet of life,and their role in the sociomateriality of the cell,which provides a novel dimension of medical science-glycomedicine.展开更多
The main protease(M^(pro))is essential for the replication of SARS-COV-2 and therefore represents a promising anti-viral target.In this study,we screened M^(pro)inhibitory peptides from Ulva prolifera protein on in-si...The main protease(M^(pro))is essential for the replication of SARS-COV-2 and therefore represents a promising anti-viral target.In this study,we screened M^(pro)inhibitory peptides from Ulva prolifera protein on in-silico proteolysis.Cytotoxicity analysis using the online toxic prediction tool ToxinPred revealed that all the peptides were non-cytotoxic.The hexapeptide(SSGFID)exhibited high M^(pro)inhibitory activity in molecular docking and its IC_(50)value was 139.40±0.82μmol/L in vitro according to fluorescence resonance energy transfer assay(FRET).Quantitative real-time(qRT-)PCR results show that SSGFID could stimulate the expression of mitosis-related factors,including nuclear factor-κB,cyclin D1,and cyclin-dependent kinase 4,to promote the proliferation of mice splenocytes.Stability study revealed that SSGFID showed resistance against pepsin and trypsin but lost D(Asp)after pretreatment at121℃ for 15 min.Besides,SSGFID was mainly transported through the Caco-2 cell monolayer by the peptide transporter PepT1 and passive-mediated transport during the transport study.Unfortunately,the peptide was also degraded by Caco-2 intracellular enzymes,and the transfer rate of intact peptide was4.2%.Furthermore,Lineweaver–Burk plots demonstrated that SSGFID possessed a mixed inhibitory characteristic with M^(pro).Our study indicated the potential of Ulva prolifera as antiviral and immuneenhancing functional food ingredients and nutraceuticals.展开更多
Most human-secreted and membrane-bound proteins have covalently attached oligosaccharide chains or glycans.Glycosylation influences the physical and chemical properties of proteins,as well as their biological function...Most human-secreted and membrane-bound proteins have covalently attached oligosaccharide chains or glycans.Glycosylation influences the physical and chemical properties of proteins,as well as their biological functions.Unsurprisingly,alterations in protein glycosylation have been implicated in a growing number of human diseases,and glycans are increasingly being considered as potential therapeutic targets,an essential part of therapeutics,and biomarkers.Although glycosylation pathways are biochemically well-studied,little is known about the networks of genes that guide the cell-and tissue-specific regulation of these biochemical reactions in humans in vivo.The lack of a detailed understanding of the mechanisms regulating glycome variation and linking the glycome to human health and disease is slowing progress in clinical applications of human glycobiology.Two of the tools that can provide much sought-after knowledge of human in vivo glycobiology are human genetics and genomics,which offer a powerful data-driven agnostic approach for dissecting the biology of complex traits.This review summarizes the current state of human populational glycogenomics.In Section 1,we provide a brief overview of the N-glycan’s structural organization,and in Section 2,we give a description of the major blood plasma glycoproteins.Next,in Section 3,we summarize,systemize,and generalize the results from current N-glycosylation genome-wide association studies(GWASs)that provide novel knowledge of the genetic regulation of the populational variation of glycosylation.Until now,such studies have been limited to an analysis of the human blood plasma N-glycome and the N-glycosylation of immunoglobulin G and transferrin.While these three glycomes make up a rather limited set compared with the enormous multitude of glycomes of different tissues and glycoproteins,the study of these three does allow for powerful analysis and generalization.Finally,in Section 4,we turn to genes in the established loci,paying particular attention to genes with strong support in Section 5.At the end of the review,in Sections 6 and 7,we describe special cases of interest in light of new discoveries,focusing on possible mechanisms of action and biological targets of genetic variation that have been implicated in human protein N-glycosylation.展开更多
2023年3月2日,浙江大学医学院张岩教授团队联合山东大学于晓、孙金鹏、冯世庆教授团队在《科学》(Science)发表了最新的研究成果“Unsaturated bond recognition leads to biased signal in a fatty acid receptor”(DOI:10.1126/scienc...2023年3月2日,浙江大学医学院张岩教授团队联合山东大学于晓、孙金鹏、冯世庆教授团队在《科学》(Science)发表了最新的研究成果“Unsaturated bond recognition leads to biased signal in a fatty acid receptor”(DOI:10.1126/science.add6220),成功从原子分辨率水平解析了脂肪酸受体GPR120形成信号转导复合物的精细三维结构,揭示了不同脂肪酸引发GPR120产生下游特定信号谱图的机制。展开更多
2022年12月28日,浙江大学基础医学院易聪研究员团队在《美国国家科学院院刊》(PNAS)发表了题为“Mec1regulates PAS recruitment of Atg13 via direct binding with Atg13 during glucose starvation-induced autophagy”的研究论文(DOI...2022年12月28日,浙江大学基础医学院易聪研究员团队在《美国国家科学院院刊》(PNAS)发表了题为“Mec1regulates PAS recruitment of Atg13 via direct binding with Atg13 during glucose starvation-induced autophagy”的研究论文(DOI:10.1073/pnas.2215126120),阐述了DNA损伤感受器Mec1调控能量匮乏诱导自噬的分子机制。研究人员用三种不同的荧光标记线粒体、Mec1和自噬体后发现,葡萄糖饥饿时,Mec1 puncta处于线粒体和自噬体互作的接触位点上,当敲低Mec1,线粒体和自噬体的距离明显增大。之后通过一系列酵母双杂交、体外拉下和免疫共沉淀实验证实,自噬前体蛋白Atg13与Mec1存在直接互作,并发现Atg13和Mec1的结合区域。对结合区域进行缺失或突变,在缺乏葡萄糖的环境里,Mec1和Atg13招募到自噬前体均受到极大的抑制。展开更多
文摘2024年1月3日,浙江大学生命科学研究院陆华松研究员与杨兵研究员团队合作在《自然·细胞生物学》(Nature Cell Biology)发表题为“A chaperone-like function of FUS ensures TAZ condensate dynamics and transcriptional activation”的研究论文(DOI:10.1038/s41556-023-01309-3),揭示了生物大分子凝聚体物质属性与其功能维持的紧密联系,发现FUS具有“分子伴侣样”的新功能,能够维持TAZ凝聚体的流动性,从而促进其转录活性的重要功能。
文摘SIRT1(Sirtuin type 1)作为Sirtuins家族最重要的成员之一,具有去乙酰化酶活性,不仅参与代谢、能量感应途径、昼夜节律机制和炎症等过程,而且作为一种表观遗传修饰物,影响DNA的损伤修复及染色体的稳定。除了参与体内众多基因转录及能量代谢外,SIRT1还可以调节细胞的衰老过程,改善或延缓与年龄相关的疾病进程。SIRT1基因多态性可作为治疗不同疾病的靶点,与多种人类相关疾病的发病机制有关,本文将对SIRT1基因多态性与相关疾病的关系作一综述。
文摘深度学习方法已经彻底改变了蛋白质结构预测和设计,但目前仅限于蛋白质系统。研究人员描述了RoseT‐TAFold All Atom(RFAA),它可以将氨基酸和DNA碱基的基于残基的表示符号与所有其他基团的原子表示符号相结合,从而对给定序列和化学结构的包含蛋白质、核酸、小分子、金属和共价修饰的组件进行建模。通过对去噪任务进行微调,科学家们获得了RFdiffusionAA,它能围绕小分子构建蛋白质结构。从围绕目标小分子的氨基酸残基的随机分布开始,研究人员通过晶体学和结合测量学,设计并实验验证了与心脏病治疗药物地高辛、酶促辅因子血红素和光捕获分子bilin结合的蛋白质。
文摘Life requires more than nucleic acids and proteins;sweet sugar molec ules could be ano ther life code beyond the central dogma of molecular biology.There are four equally important major building blocks of life:nucleic acids(DNA and RNA),proteins,carbohydrates(glycans),and lipids.The first two are also known as the first and second alphabets of biology,following the principle of the"central dogma"of transcription(DNA to RNA)and trahslation(RNA to protein).However,the latter two crucial components,glycans and lipids,are missing from biology's central dogma Regarding the communi-cation between glycans and lipids,there may be a yet-to-be-discovered law:Does a paracentral dogma exist?This commentary focuses on glycans,the third alphabet of life,and their role in the sociomateriality of the cell,which provides a novel dimension of medical science-glycomedicine.
基金Supported by the National Key R&D Program of China (No.2016YFC1402102)the National Natural Science Foundation of China (No.41976109)the Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)。
文摘The main protease(M^(pro))is essential for the replication of SARS-COV-2 and therefore represents a promising anti-viral target.In this study,we screened M^(pro)inhibitory peptides from Ulva prolifera protein on in-silico proteolysis.Cytotoxicity analysis using the online toxic prediction tool ToxinPred revealed that all the peptides were non-cytotoxic.The hexapeptide(SSGFID)exhibited high M^(pro)inhibitory activity in molecular docking and its IC_(50)value was 139.40±0.82μmol/L in vitro according to fluorescence resonance energy transfer assay(FRET).Quantitative real-time(qRT-)PCR results show that SSGFID could stimulate the expression of mitosis-related factors,including nuclear factor-κB,cyclin D1,and cyclin-dependent kinase 4,to promote the proliferation of mice splenocytes.Stability study revealed that SSGFID showed resistance against pepsin and trypsin but lost D(Asp)after pretreatment at121℃ for 15 min.Besides,SSGFID was mainly transported through the Caco-2 cell monolayer by the peptide transporter PepT1 and passive-mediated transport during the transport study.Unfortunately,the peptide was also degraded by Caco-2 intracellular enzymes,and the transfer rate of intact peptide was4.2%.Furthermore,Lineweaver–Burk plots demonstrated that SSGFID possessed a mixed inhibitory characteristic with M^(pro).Our study indicated the potential of Ulva prolifera as antiviral and immuneenhancing functional food ingredients and nutraceuticals.
基金an output of a research project implemented as part of the Research Program at the Moscow State University (MSU) Institute for Artificial Intelligence.
文摘Most human-secreted and membrane-bound proteins have covalently attached oligosaccharide chains or glycans.Glycosylation influences the physical and chemical properties of proteins,as well as their biological functions.Unsurprisingly,alterations in protein glycosylation have been implicated in a growing number of human diseases,and glycans are increasingly being considered as potential therapeutic targets,an essential part of therapeutics,and biomarkers.Although glycosylation pathways are biochemically well-studied,little is known about the networks of genes that guide the cell-and tissue-specific regulation of these biochemical reactions in humans in vivo.The lack of a detailed understanding of the mechanisms regulating glycome variation and linking the glycome to human health and disease is slowing progress in clinical applications of human glycobiology.Two of the tools that can provide much sought-after knowledge of human in vivo glycobiology are human genetics and genomics,which offer a powerful data-driven agnostic approach for dissecting the biology of complex traits.This review summarizes the current state of human populational glycogenomics.In Section 1,we provide a brief overview of the N-glycan’s structural organization,and in Section 2,we give a description of the major blood plasma glycoproteins.Next,in Section 3,we summarize,systemize,and generalize the results from current N-glycosylation genome-wide association studies(GWASs)that provide novel knowledge of the genetic regulation of the populational variation of glycosylation.Until now,such studies have been limited to an analysis of the human blood plasma N-glycome and the N-glycosylation of immunoglobulin G and transferrin.While these three glycomes make up a rather limited set compared with the enormous multitude of glycomes of different tissues and glycoproteins,the study of these three does allow for powerful analysis and generalization.Finally,in Section 4,we turn to genes in the established loci,paying particular attention to genes with strong support in Section 5.At the end of the review,in Sections 6 and 7,we describe special cases of interest in light of new discoveries,focusing on possible mechanisms of action and biological targets of genetic variation that have been implicated in human protein N-glycosylation.
文摘2023年3月2日,浙江大学医学院张岩教授团队联合山东大学于晓、孙金鹏、冯世庆教授团队在《科学》(Science)发表了最新的研究成果“Unsaturated bond recognition leads to biased signal in a fatty acid receptor”(DOI:10.1126/science.add6220),成功从原子分辨率水平解析了脂肪酸受体GPR120形成信号转导复合物的精细三维结构,揭示了不同脂肪酸引发GPR120产生下游特定信号谱图的机制。
文摘2022年12月28日,浙江大学基础医学院易聪研究员团队在《美国国家科学院院刊》(PNAS)发表了题为“Mec1regulates PAS recruitment of Atg13 via direct binding with Atg13 during glucose starvation-induced autophagy”的研究论文(DOI:10.1073/pnas.2215126120),阐述了DNA损伤感受器Mec1调控能量匮乏诱导自噬的分子机制。研究人员用三种不同的荧光标记线粒体、Mec1和自噬体后发现,葡萄糖饥饿时,Mec1 puncta处于线粒体和自噬体互作的接触位点上,当敲低Mec1,线粒体和自噬体的距离明显增大。之后通过一系列酵母双杂交、体外拉下和免疫共沉淀实验证实,自噬前体蛋白Atg13与Mec1存在直接互作,并发现Atg13和Mec1的结合区域。对结合区域进行缺失或突变,在缺乏葡萄糖的环境里,Mec1和Atg13招募到自噬前体均受到极大的抑制。
