Crystal structure of aura virus capsid protease and its complex with dioxane: new insights into capsid-glycoprotein molecular contacts
The nucleocapsid core interaction with endodomains of glycoproteins plays a critical role in the alphavirus life cycle that is essential to virus budding. Recent cryo-electron microscopy (cryo-EM) studies provide structural insights into key interactions between capsid protein (CP) and trans-membran...
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| creator | Aggarwal, Megha Tapas, Satya Preeti Siwach, Anjul Kumar, Pravindra Kuhn, Richard J Tomar, Shailly |
| description | The nucleocapsid core interaction with endodomains of glycoproteins plays a critical role in the alphavirus life cycle that is essential to virus budding. Recent cryo-electron microscopy (cryo-EM) studies provide structural insights into key interactions between capsid protein (CP) and trans-membrane glycoproteins E1 and E2. CP possesses a chymotrypsin-like fold with a hydrophobic pocket at the surface responsible for interaction with glycoproteins. In the present study, crystal structures of the protease domain of CP from Aura virus and its complex with dioxane were determined at 1.81 and 1.98 Å resolution respectively. Due to the absence of crystal structures, homology models of E1 and E2 from Aura virus were generated. The crystal structure of CP and structural models of E1 and E2 were fitted into the cryo-EM density map of Venezuelan equine encephalitis virus (VEEV) for detailed analysis of CP-glycoprotein interactions. Structural analysis revealed that the E2 endodomain consists of a helix-loop-helix motif where the loop region fits into the hydrophobic pocket of CP. Our studies suggest that Cys397, Cys418 and Tyr401 residues of E2 are involved in stabilizing the structure of E2 endodomain. Density map fitting analysis revealed that Pro405, a conserved E2 residue is present in the loop region of the E2 endodomain helix-loop-helix structure and makes intermolecular hydrophobic contacts with the capsid. In the Aura virus capsid protease (AVCP)-dioxane complex structure, dioxane occupies the hydrophobic pocket on CP and structurally mimics the hydrophobic pyrollidine ring of Pro405 in the loop region of E2. |
| doi_str_mv | 10.1371/journal.pone.0051288 |
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Recent cryo-electron microscopy (cryo-EM) studies provide structural insights into key interactions between capsid protein (CP) and trans-membrane glycoproteins E1 and E2. CP possesses a chymotrypsin-like fold with a hydrophobic pocket at the surface responsible for interaction with glycoproteins. In the present study, crystal structures of the protease domain of CP from Aura virus and its complex with dioxane were determined at 1.81 and 1.98 Å resolution respectively. Due to the absence of crystal structures, homology models of E1 and E2 from Aura virus were generated. The crystal structure of CP and structural models of E1 and E2 were fitted into the cryo-EM density map of Venezuelan equine encephalitis virus (VEEV) for detailed analysis of CP-glycoprotein interactions. Structural analysis revealed that the E2 endodomain consists of a helix-loop-helix motif where the loop region fits into the hydrophobic pocket of CP. Our studies suggest that Cys397, Cys418 and Tyr401 residues of E2 are involved in stabilizing the structure of E2 endodomain. Density map fitting analysis revealed that Pro405, a conserved E2 residue is present in the loop region of the E2 endodomain helix-loop-helix structure and makes intermolecular hydrophobic contacts with the capsid. In the Aura virus capsid protease (AVCP)-dioxane complex structure, dioxane occupies the hydrophobic pocket on CP and structurally mimics the hydrophobic pyrollidine ring of Pro405 in the loop region of E2.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0051288</identifier><identifier>PMID: 23251484</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Acids ; Alphavirus - enzymology ; Amino Acid Sequence ; Biology ; Biotechnology ; Budding ; Capsid protein ; Chymotrypsin ; Crystal structure ; Dioxane ; Dioxanes - chemistry ; Electron microscopy ; Encephalitis ; Glycoproteins ; Glycoproteins - chemistry ; Helix-loop-helix ; Helix-loop-helix proteins ; Homology ; Hydrophobicity ; Life cycle engineering ; Life cycles ; Membrane glycoproteins ; Membrane proteins ; Models, Molecular ; Molecular Sequence Data ; Mutation ; Nucleocapsids ; Peptide Hydrolases - chemistry ; Protease ; Proteases ; Protein Conformation ; Proteinase ; Proteins ; Sequence Homology, Amino Acid ; Structural analysis ; Structural models ; Studies ; Venezuelan equine encephalitis ; Viral proteins ; Viruses</subject><ispartof>PloS one, 2012-12, Vol.7 (12), p.e51288-e51288</ispartof><rights>COPYRIGHT 2012 Public Library of Science</rights><rights>2012 Aggarwal et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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Recent cryo-electron microscopy (cryo-EM) studies provide structural insights into key interactions between capsid protein (CP) and trans-membrane glycoproteins E1 and E2. CP possesses a chymotrypsin-like fold with a hydrophobic pocket at the surface responsible for interaction with glycoproteins. In the present study, crystal structures of the protease domain of CP from Aura virus and its complex with dioxane were determined at 1.81 and 1.98 Å resolution respectively. Due to the absence of crystal structures, homology models of E1 and E2 from Aura virus were generated. The crystal structure of CP and structural models of E1 and E2 were fitted into the cryo-EM density map of Venezuelan equine encephalitis virus (VEEV) for detailed analysis of CP-glycoprotein interactions. Structural analysis revealed that the E2 endodomain consists of a helix-loop-helix motif where the loop region fits into the hydrophobic pocket of CP. Our studies suggest that Cys397, Cys418 and Tyr401 residues of E2 are involved in stabilizing the structure of E2 endodomain. Density map fitting analysis revealed that Pro405, a conserved E2 residue is present in the loop region of the E2 endodomain helix-loop-helix structure and makes intermolecular hydrophobic contacts with the capsid. 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enzymology</topic><topic>Amino Acid Sequence</topic><topic>Biology</topic><topic>Biotechnology</topic><topic>Budding</topic><topic>Capsid protein</topic><topic>Chymotrypsin</topic><topic>Crystal structure</topic><topic>Dioxane</topic><topic>Dioxanes - chemistry</topic><topic>Electron microscopy</topic><topic>Encephalitis</topic><topic>Glycoproteins</topic><topic>Glycoproteins - chemistry</topic><topic>Helix-loop-helix</topic><topic>Helix-loop-helix proteins</topic><topic>Homology</topic><topic>Hydrophobicity</topic><topic>Life cycle engineering</topic><topic>Life cycles</topic><topic>Membrane glycoproteins</topic><topic>Membrane proteins</topic><topic>Models, Molecular</topic><topic>Molecular Sequence Data</topic><topic>Mutation</topic><topic>Nucleocapsids</topic><topic>Peptide Hydrolases - chemistry</topic><topic>Protease</topic><topic>Proteases</topic><topic>Protein Conformation</topic><topic>Proteinase</topic><topic>Proteins</topic><topic>Sequence Homology, Amino Acid</topic><topic>Structural analysis</topic><topic>Structural models</topic><topic>Studies</topic><topic>Venezuelan equine encephalitis</topic><topic>Viral proteins</topic><topic>Viruses</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Aggarwal, Megha</creatorcontrib><creatorcontrib>Tapas, Satya</creatorcontrib><creatorcontrib>Preeti</creatorcontrib><creatorcontrib>Siwach, Anjul</creatorcontrib><creatorcontrib>Kumar, Pravindra</creatorcontrib><creatorcontrib>Kuhn, Richard J</creatorcontrib><creatorcontrib>Tomar, Shailly</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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Recent cryo-electron microscopy (cryo-EM) studies provide structural insights into key interactions between capsid protein (CP) and trans-membrane glycoproteins E1 and E2. CP possesses a chymotrypsin-like fold with a hydrophobic pocket at the surface responsible for interaction with glycoproteins. In the present study, crystal structures of the protease domain of CP from Aura virus and its complex with dioxane were determined at 1.81 and 1.98 Å resolution respectively. Due to the absence of crystal structures, homology models of E1 and E2 from Aura virus were generated. The crystal structure of CP and structural models of E1 and E2 were fitted into the cryo-EM density map of Venezuelan equine encephalitis virus (VEEV) for detailed analysis of CP-glycoprotein interactions. Structural analysis revealed that the E2 endodomain consists of a helix-loop-helix motif where the loop region fits into the hydrophobic pocket of CP. Our studies suggest that Cys397, Cys418 and Tyr401 residues of E2 are involved in stabilizing the structure of E2 endodomain. Density map fitting analysis revealed that Pro405, a conserved E2 residue is present in the loop region of the E2 endodomain helix-loop-helix structure and makes intermolecular hydrophobic contacts with the capsid. In the Aura virus capsid protease (AVCP)-dioxane complex structure, dioxane occupies the hydrophobic pocket on CP and structurally mimics the hydrophobic pyrollidine ring of Pro405 in the loop region of E2.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23251484</pmid><doi>10.1371/journal.pone.0051288</doi><tpages>e51288</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2012-12, Vol.7 (12), p.e51288-e51288 |
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| subjects | Acids Alphavirus - enzymology Amino Acid Sequence Biology Biotechnology Budding Capsid protein Chymotrypsin Crystal structure Dioxane Dioxanes - chemistry Electron microscopy Encephalitis Glycoproteins Glycoproteins - chemistry Helix-loop-helix Helix-loop-helix proteins Homology Hydrophobicity Life cycle engineering Life cycles Membrane glycoproteins Membrane proteins Models, Molecular Molecular Sequence Data Mutation Nucleocapsids Peptide Hydrolases - chemistry Protease Proteases Protein Conformation Proteinase Proteins Sequence Homology, Amino Acid Structural analysis Structural models Studies Venezuelan equine encephalitis Viral proteins Viruses |
| title | Crystal structure of aura virus capsid protease and its complex with dioxane: new insights into capsid-glycoprotein molecular contacts |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-13T20%3A55%3A18IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Crystal%20structure%20of%20aura%20virus%20capsid%20protease%20and%20its%20complex%20with%20dioxane:%20new%20insights%20into%20capsid-glycoprotein%20molecular%20contacts&rft.jtitle=PloS%20one&rft.au=Aggarwal,%20Megha&rft.date=2012-12-14&rft.volume=7&rft.issue=12&rft.spage=e51288&rft.epage=e51288&rft.pages=e51288-e51288&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0051288&rft_dat=%3Cgale_plos_%3EA477083472%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1327136938&rft_id=info:pmid/23251484&rft_galeid=A477083472&rft_doaj_id=oai_doaj_org_article_f2d1cb1fc8bb43e29a6690bf86e89227&rfr_iscdi=true |