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Article: Functional Constraint Profiling of a Viral Protein Reveals Discordance of Evolutionary Conservation and Functionality

TitleFunctional Constraint Profiling of a Viral Protein Reveals Discordance of Evolutionary Conservation and Functionality
Authors
Issue Date2015
Citation
PLoS Genetics, 2015, v. 11, n. 7, article no. e1005310 How to Cite?
Abstract© 2015 Wu et al. Viruses often encode proteins with multiple functions due to their compact genomes. Existing approaches to identify functional residues largely rely on sequence conservation analysis. Inferring functional residues from sequence conservation can produce false positives, in which the conserved residues are functionally silent, or false negatives, where functional residues are not identified since they are species-specific and therefore non-conserved. Furthermore, the tedious process of constructing and analyzing individual mutations limits the number of residues that can be examined in a single study. Here, we developed a systematic approach to identify the functional residues of a viral protein by coupling experimental fitness profiling with protein stability prediction using the influenza virus polymerase PA subunit as the target protein. We identified a significant number of functional residues that were influenza type-specific and were evolutionarily non-conserved among different influenza types. Our results indicate that type-specific functional residues are prevalent and may not otherwise be identified by sequence conservation analysis alone. More importantly, this technique can be adapted to any viral (and potentially non-viral) protein where structural information is available.
Persistent Identifierhttp://hdl.handle.net/10722/285530
ISSN
2014 Impact Factor: 7.528
2023 SCImago Journal Rankings: 2.219
PubMed Central ID
ISI Accession Number ID
Errata

 

DC FieldValueLanguage
dc.contributor.authorWu, Nicholas C.-
dc.contributor.authorOlson, C. Anders-
dc.contributor.authorDu, Yushen-
dc.contributor.authorLe, Shuai-
dc.contributor.authorTran, Kevin-
dc.contributor.authorRemenyi, Roland-
dc.contributor.authorGong, Danyang-
dc.contributor.authorAl-Mawsawi, Laith Q.-
dc.contributor.authorQi, Hangfei-
dc.contributor.authorWu, Ting Ting-
dc.contributor.authorSun, Ren-
dc.date.accessioned2020-08-18T04:55:59Z-
dc.date.available2020-08-18T04:55:59Z-
dc.date.issued2015-
dc.identifier.citationPLoS Genetics, 2015, v. 11, n. 7, article no. e1005310-
dc.identifier.issn1553-7390-
dc.identifier.urihttp://hdl.handle.net/10722/285530-
dc.description.abstract© 2015 Wu et al. Viruses often encode proteins with multiple functions due to their compact genomes. Existing approaches to identify functional residues largely rely on sequence conservation analysis. Inferring functional residues from sequence conservation can produce false positives, in which the conserved residues are functionally silent, or false negatives, where functional residues are not identified since they are species-specific and therefore non-conserved. Furthermore, the tedious process of constructing and analyzing individual mutations limits the number of residues that can be examined in a single study. Here, we developed a systematic approach to identify the functional residues of a viral protein by coupling experimental fitness profiling with protein stability prediction using the influenza virus polymerase PA subunit as the target protein. We identified a significant number of functional residues that were influenza type-specific and were evolutionarily non-conserved among different influenza types. Our results indicate that type-specific functional residues are prevalent and may not otherwise be identified by sequence conservation analysis alone. More importantly, this technique can be adapted to any viral (and potentially non-viral) protein where structural information is available.-
dc.languageeng-
dc.relation.ispartofPLoS Genetics-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleFunctional Constraint Profiling of a Viral Protein Reveals Discordance of Evolutionary Conservation and Functionality-
dc.typeArticle-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1371/journal.pgen.1005310-
dc.identifier.pmid26132554-
dc.identifier.pmcidPMC4489113-
dc.identifier.scopuseid_2-s2.0-84938795335-
dc.identifier.volume11-
dc.identifier.issue7-
dc.identifier.spagearticle no. e1005310-
dc.identifier.epagearticle no. e1005310-
dc.identifier.eissn1553-7404-
dc.identifier.isiWOS:000360622200012-
dc.relation.erratumdoi:10.1371/journal.pgen.1006709-
dc.identifier.issnl1553-7390-

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