PDB-6lhc: The cryo-EM structure of coxsackievirus A16 empty particle

基本情報

• 登録情報: データベース: PDB / ID: 6lhc
• タイトル: The cryo-EM structure of coxsackievirus A16 empty particle

要素

• VP1
• VP2
• VP3

• キーワード: VIRUS

機能・相同性

分子機能:

symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MDA-5 activity / picornain 2A / symbiont-mediated suppression of host mRNA export from nucleus / symbiont genome entry into host cell via pore formation in plasma membrane / picornain 3C / T=pseudo3 icosahedral viral capsid / host cell cytoplasmic vesicle membrane / cytoplasmic vesicle membrane / endocytosis involved in viral entry into host cell / viral capsid / nucleoside-triphosphate phosphatase / protein complex oligomerization / monoatomic ion channel activity / symbiont-mediated suppression of host gene expression / DNA replication / RNA helicase activity / induction by virus of host autophagy / RNA-directed RNA polymerase / viral RNA genome replication / cysteine-type endopeptidase activity / RNA-dependent RNA polymerase activity / virus-mediated perturbation of host defense response / DNA-templated transcription / host cell nucleus / virion attachment to host cell / structural molecule activity / ATP hydrolysis activity / proteolysis / RNA binding / ATP binding / membrane / metal ion binding

ドメイン・相同性:

Jelly Rolls - #20 / Poliovirus 3A protein-like / Poliovirus 3A protein like / Picornavirus 2B protein / Poliovirus core protein 3a, soluble domain / Picornavirus 2B protein / Peptidase C3, picornavirus core protein 2A / Picornavirus core protein 2A / Picornavirus coat protein VP4 / Picornavirus coat protein (VP4) / Picornavirales 3C/3C-like protease domain / Picornavirales 3C/3C-like protease domain profile. / Peptidase C3A/C3B, picornaviral / 3C cysteine protease (picornain 3C) / Picornavirus capsid / picornavirus capsid protein / Helicase, superfamily 3, single-stranded RNA virus / Superfamily 3 helicase of positive ssRNA viruses domain profile. / Helicase, superfamily 3, single-stranded DNA/RNA virus / RNA helicase / Picornavirus/Calicivirus coat protein / Viral coat protein subunit / RNA-directed RNA polymerase, C-terminal domain / Viral RNA-dependent RNA polymerase / Reverse transcriptase/Diguanylate cyclase domain / Jelly Rolls / RNA-directed RNA polymerase, catalytic domain / RdRp of positive ssRNA viruses catalytic domain profile. / ATPases associated with a variety of cellular activities / AAA+ ATPase domain / Peptidase S1, PA clan, chymotrypsin-like fold / Peptidase S1, PA clan / DNA/RNA polymerase superfamily / Sandwich / P-loop containing nucleoside triphosphate hydrolase / Mainly Beta

構成要素:

Genome polyprotein / Genome polyprotein / Genome polyprotein / Genome polyprotein

• 生物種: Coxsackievirus A16 (コクサッキーウイルス)
• 手法: 電子顕微鏡法 / 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.43 Å
• データ登録者: He, M.Z. / Xu, L.F. / Zheng, Q.B. / Zhu, R. / Yin, Z.C. / Cheng, T. / Li, S.W.

資金援助

中国, 米国, 9件

組織	認可番号	国
National Natural Science Foundation of China	81991490	中国
National Science Foundation (China)	2018ZX09711003-005-003	中国
National Science Foundation (China)	2017ZX10304402-002-003	中国
National Natural Science Foundation of China	31670933	中国
National Natural Science Foundation of China	81801646	中国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)	R37-GM33050	米国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)	GM071940	米国
National Institutes of Health/National Institute of Dental and Craniofacial Research (NIH/NIDCR)	DE025567	米国
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)	AI094386	米国

• 引用: ジャーナル: Cell Host Microbe / 年: 2020; タイトル: Identification of Antibodies with Non-overlapping Neutralization Sites that Target Coxsackievirus A16.; 著者: Maozhou He / Longfa Xu / Qingbing Zheng / Rui Zhu / Zhichao Yin / Zhenghui Zha / Yu Lin / Lisheng Yang / Yang Huang / Xiangzhong Ye / Shuxuan Li / Wangheng Hou / Yangtao Wu / Jinle Han / Dongxiao Liu / Zekai Li / Zhenqin Chen / Hai Yu / Yuqiong Que / Yingbin Wang / Xiaodong Yan / Jun Zhang / Ying Gu / Z Hong Zhou / Tong Cheng / Shaowei Li / Ningshao Xia / ; 要旨: Hand, foot, and mouth disease is a common childhood illness primarily caused by coxsackievirus A16 (CVA16), for which there are no current vaccines or treatments. We identify three CVA16-specific neutralizing monoclonal antibodies (nAbs) with therapeutic potential: 18A7, 14B10, and NA9D7. We present atomic structures of these nAbs bound to all three viral particle forms-the mature virion, A-particle, and empty particle-and show that each Fab can simultaneously occupy the mature virion. Additionally, 14B10 or NA9D7 provide 100% protection against lethal CVA16 infection in a neonatal mouse model. 18A7 binds to a non-conserved epitope present in all three particles, whereas 14B10 and NA9D7 recognize broad protective epitopes but only bind the mature virion. NA9D7 targets an immunodominant site, which may overlap the receptor-binding site. These findings indicate that CVA16 vaccines should be based on mature virions and that these antibodies could be used to discriminate optimal virion-based immunogens.

履歴

登録	2019年12月7日	登録サイト: PDBJ / 処理サイト: PDBJ
改定 1.0	2020年2月5日	Provider: repository / タイプ: Initial release
改定 1.1	2020年2月19日	Group: Database references / カテゴリ: citation / citation_author / Item: _citation.pdbx_database_id_PubMed / _citation.title
改定 1.2	2020年2月26日	Group: Database references / カテゴリ: citation / Item: _citation.journal_volume / _citation.page_first
改定 1.3	2022年3月23日	Group: Author supporting evidence / Database references / Derived calculations カテゴリ: database_2 / pdbx_audit_support / pdbx_struct_oper_list Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_audit_support.funding_organization / _pdbx_struct_oper_list.name / _pdbx_struct_oper_list.symmetry_operation / _pdbx_struct_oper_list.type
改定 1.4	2024年5月29日	Group: Data collection / カテゴリ: chem_comp_atom / chem_comp_bond