Show simple item record

Files in this item

Thumbnail

Item metadata

dc.contributor.authorPotter, Jane A.
dc.contributor.authorRandall, Richard Edward
dc.contributor.authorTaylor, Garry L.
dc.date.accessioned2010-11-01T15:34:17Z
dc.date.available2010-11-01T15:34:17Z
dc.date.issued2008-02-28
dc.identifier.citationPotter , J A , Randall , R E & Taylor , G L 2008 , ' Crystal structure of human IPS-1/MAVS/VISA/Cardif caspase activation recruitment domain ' , BMC Structural Biology , vol. 8 , no. 11 , 11 . https://doi.org/10.1186/1472-6807-8-11en
dc.identifier.issn1472-6807
dc.identifier.otherPURE: 617509
dc.identifier.otherPURE UUID: 49862c86-a3da-45ca-9357-72d5db6ecc01
dc.identifier.otherWOS: 000254711100001
dc.identifier.otherScopus: 41849132440
dc.identifier.otherORCID: /0000-0002-9304-6678/work/60427031
dc.identifier.otherORCID: /0000-0001-9486-566X/work/60428048
dc.identifier.urihttp://hdl.handle.net/10023/1192
dc.description.abstractBackground: IPS-1/MAVS/VISA/Cardif is an adaptor protein that plays a crucial role in the induction of interferons in response to viral infection. In the initial stage of the intracellular antiviral response two RNA helicases, retinoic acid inducible gene-I (RIG-I) and melanoma differentiation-association gene 5 (MDA5), are independently able to bind viral RNA in the cytoplasm. The 62 kDa protein IPS-1/MAVS/VISA/Cardif contains an N-terminal caspase activation and recruitment (CARD) domain that associates with the CARD regions of RIG-I and MDA5, ultimately leading to the induction of type I interferons. As a first step towards understanding the molecular basis of this important adaptor protein we have undertaken structural studies of the IPS-1 MAVS/VISA/Cardif CARD region. Results: The crystal structure of human IPS-1/MAVS/VISA/Cardif CARD has been determined to 2.1 angstrom resolution. The protein was expressed and crystallized as a maltose-binding protein (MBP) fusion protein. The MBP and IPS-1 components each form a distinct domain within the structure. IPS-1/MAVS/VISA/Cardif CARD adopts a characteristic six-helix bundle with a Greek-key topology and, in common with a number of other known CARD structures, contains two major polar surfaces on opposite sides of the molecule. One face has a surface-exposed, disordered tryptophan residue that may explain the poor solubility of untagged expression constructs. Conclusion: The IPS-1/MAVS/VISA/Cardif CARD domain adopts the classic CARD fold with an asymmetric surface charge distribution that is typical of CARD domains involved in homotypic protein-protein interactions. The location of the two polar areas on IPS-1/MAVS/VISA/Cardif CARD suggest possible types of associations that this domain makes with the two CARD domains of MDA5 or RIG-I. The N-terminal CARD domains of RIG-I and MDA5 share greatest sequence similarity with IPS-1/MAVS/VISA/Cardif CARD and this has allowed modelling of their structures. These models show a very different charge profile for the equivalent surfaces compared to IPS-1/MAVS/VISA/Cardif CARD.
dc.format.extent10
dc.language.isoeng
dc.relation.ispartofBMC Structural Biologyen
dc.rights© 2008 Potter et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.en
dc.subjectRIG-Ien
dc.subjectAntiviral responsesen
dc.subjectAdapter proteinen
dc.subjectInnate immunityen
dc.subjectRNA helicaseen
dc.subjectIKK-epsolinen
dc.subjectInterferonen
dc.subjectVirusen
dc.subjectModelen
dc.subjectDeathen
dc.subjectQR355 Virologyen
dc.subject.lccQR355en
dc.titleCrystal structure of human IPS-1/MAVS/VISA/Cardif caspase activation recruitment domainen
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews.School of Biologyen
dc.contributor.institutionUniversity of St Andrews.Biomedical Sciences Research Complexen
dc.identifier.doihttps://doi.org/10.1186/1472-6807-8-11
dc.description.statusPeer revieweden
dc.identifier.urlhttp://www.scopus.com/inward/record.url?scp=41849132440&partnerID=8YFLogxKen


This item appears in the following Collection(s)

Show simple item record