%0 Journal Article
%T Crystal structure of human IPS-1/MAVS/VISA/Cardif caspase activation recruitment domain
%A Jane A Potter
%A Richard E Randall
%A Garry L Taylor
%J BMC Structural Biology
%D 2008
%I BioMed Central
%R 10.1186/1472-6807-8-11
%X The crystal structure of human IPS-1/MAVS/VISA/Cardif CARD has been determined to 2.1£¿ 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.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.In the cells of higher eukaryotes, recognition of virally-derived RNA intermediates produced during replication activates signalling cascades that trigger the production of interferons (IFNs) and other cytokines, which in turn mediate innate immunity and modulate subsequent adaptive immunity [1,2]. The innate immune system utilizes pattern-recognition receptors (PRRs) to detect conserved molecular patterns on certain types of molecule that are not produced by the host but are characterisitic of invading microorganisms [3]. There are two categories of PRRs involved in the induction of type I IFNs: Toll-like receptor (TLRs) and RIG-I-like receptors (RLRs). The transmembrane-anchored TLR family members, pres
%U http://www.biomedcentral.com/1472-6807/8/11