The coronavirus disease 2019(COVID-19)pandemic has led to worldwide efforts to understand the biological traits of the newly identified human coronavirus(HCoV-19)virus.In this mass spectrometry(MS)-based study,we reve...The coronavirus disease 2019(COVID-19)pandemic has led to worldwide efforts to understand the biological traits of the newly identified human coronavirus(HCoV-19)virus.In this mass spectrometry(MS)-based study,we reveal that out of 21 possible glycosites in the HCoV-19 spike protein(S protein),20 are completely occupied by N-glycans,predominantly of the oligomannose type.All seven glycosylation sites in human angiotensin I converting enzyme 2(hACE2)were found to be completely occupied,mainly by complex N-glycans.However,glycosylation did not directly contribute to the binding affinity between HCoV-19 S protein and hACE2.Additional post-translational modification(PTM)was identified,including multiple methylated sites in both proteins and multiple sites with hydroxylproline in hACE2.Refined structural models of HCoV-19 S protein and hACE2 were built by adding N-glycan and PTMs to recently published cryogenic electron microscopy structures.The PTM and glycan maps of HCoV-19 S protein and hACE2 provide additional structural details for studying the mechanisms underlying host attachment and the immune response of HCoV-19,as well as knowledge for developing desperately needed remedies and vaccines.展开更多
Fishes are the largest group of vertebrates,representing more than half of all vertebrate species on Earth.Important aquaculture species,such as Atlantic salmon,cod,and large yellow croaker,contribute to over 16%of th...Fishes are the largest group of vertebrates,representing more than half of all vertebrate species on Earth.Important aquaculture species,such as Atlantic salmon,cod,and large yellow croaker,contribute to over 16%of the global seafood supply for human consumption(Food and Agriculture Organization of the United Nations,2020).Zebrafish(Danio rerio),medaka(Oryzias latipes),threespined stickleback(Gasterosteus aculeatus),and other fish species are important model organisms in life science research.展开更多
The devastating coronavirus disease 2019(COVID-19)pandemic has prompted worldwide efforts to study structural biological traits of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and its viral components.Co...The devastating coronavirus disease 2019(COVID-19)pandemic has prompted worldwide efforts to study structural biological traits of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and its viral components.Compared to the Spike protein,which is the primary target for currently available vaccines or antibodies,knowledge about other virion structural components is incomplete.Using high-resolution mass spectrometry,we report a comprehensive post-translational modification(PTM)analysis of nucleocapsid phosphoprotein(NCP),the most abundant structural component of the SARS-CoV-2 virion.In addition to phosphoryl groups,we show that the SARS-CoV-2 NCP is decorated with a variety of PTMs,including N-glycans and ubiquitin.Based on newly identified PTMs,refined protein structural models of SARS-CoV-2 NCP were proposed and potential immune recognition epitopes of NCP were aligned with PTMs.These data can facilitate the design of novel vaccines or therapeutics targeting NCP,as valuable alternatives to the current vaccination and treatment paradigm that is under threat of the ever-mutating SARS-CoV-2 Spike protein.展开更多
基金This work was supported by the National Key Research and Development Program(2017YFC1200204,2017YFA0504803,and 2018YFA0507700)Emergency Project of Zhejiang Provincial Department of Science and Technology(2020C03123-1)+1 种基金Fundamental Research Funds for the Central Universities(2018XZZX001-13)Independent Project Fund of the State Key Laboratory for Diagnosis and Treatment of Infectious Disease.
文摘The coronavirus disease 2019(COVID-19)pandemic has led to worldwide efforts to understand the biological traits of the newly identified human coronavirus(HCoV-19)virus.In this mass spectrometry(MS)-based study,we reveal that out of 21 possible glycosites in the HCoV-19 spike protein(S protein),20 are completely occupied by N-glycans,predominantly of the oligomannose type.All seven glycosylation sites in human angiotensin I converting enzyme 2(hACE2)were found to be completely occupied,mainly by complex N-glycans.However,glycosylation did not directly contribute to the binding affinity between HCoV-19 S protein and hACE2.Additional post-translational modification(PTM)was identified,including multiple methylated sites in both proteins and multiple sites with hydroxylproline in hACE2.Refined structural models of HCoV-19 S protein and hACE2 were built by adding N-glycan and PTMs to recently published cryogenic electron microscopy structures.The PTM and glycan maps of HCoV-19 S protein and hACE2 provide additional structural details for studying the mechanisms underlying host attachment and the immune response of HCoV-19,as well as knowledge for developing desperately needed remedies and vaccines.
基金supported by the National Key R&D Program of China(2021YFD1200804 and 2018YFD0901201)the Strategic Priority Research Program of the Chinese Academy of Sciences(Precision Seed Design and Breeding)(XDA24010206)。
文摘Fishes are the largest group of vertebrates,representing more than half of all vertebrate species on Earth.Important aquaculture species,such as Atlantic salmon,cod,and large yellow croaker,contribute to over 16%of the global seafood supply for human consumption(Food and Agriculture Organization of the United Nations,2020).Zebrafish(Danio rerio),medaka(Oryzias latipes),threespined stickleback(Gasterosteus aculeatus),and other fish species are important model organisms in life science research.
基金supported by the National Natural Science Foundation of China(U20A20343)the National Key Research and Development Program(2017YFC1200204)+1 种基金Emergency Project of Zhejiang Provincial Department of Science and Technology(2020C03123-1)Fundamental Research Funds for the Central Universities(2018XZZX001-13).
文摘The devastating coronavirus disease 2019(COVID-19)pandemic has prompted worldwide efforts to study structural biological traits of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and its viral components.Compared to the Spike protein,which is the primary target for currently available vaccines or antibodies,knowledge about other virion structural components is incomplete.Using high-resolution mass spectrometry,we report a comprehensive post-translational modification(PTM)analysis of nucleocapsid phosphoprotein(NCP),the most abundant structural component of the SARS-CoV-2 virion.In addition to phosphoryl groups,we show that the SARS-CoV-2 NCP is decorated with a variety of PTMs,including N-glycans and ubiquitin.Based on newly identified PTMs,refined protein structural models of SARS-CoV-2 NCP were proposed and potential immune recognition epitopes of NCP were aligned with PTMs.These data can facilitate the design of novel vaccines or therapeutics targeting NCP,as valuable alternatives to the current vaccination and treatment paradigm that is under threat of the ever-mutating SARS-CoV-2 Spike protein.
