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Title: Crystal structure of human IPS-1/MAVS/VISA/Cardif caspase activation recruitment domain
Authors: Potter, Jane A.
Randall, Richard Edward
Taylor, Garry L.
Keywords: RIG-I
Antiviral responses
Adapter protein
Innate immunity
RNA helicase
IKK-epsolin
Interferon
Virus
Model
Death
QR355 Virology
Issue Date: 28-Feb-2008
Citation: Potter , 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 .
Abstract: Background: 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.
Version: Publisher PDF
Status: Peer reviewed
URI: http://hdl.handle.net/10023/1192
DOI: http://dx.doi.org/10.1186/1472-6807-8-11
ISSN: 1472-6807
Type: Journal article
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.
Appears in Collections:University of St Andrews Research
Biology Research
Biomedical Sciences Research Complex (BSRC) Research



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