Structure and regulation of cytoplasmic adapter proteins involved in innate immune signaling.
Initiation of the innate immune response requires agonist recognition by a pathogen recognition receptor. Following ligand binding, conformational rearrangement of the receptor creates a molecular scaffold from which signal transduction is propagated via complex cellular signaling pathways. This in turn leads to the induction of a pro-inflammatory immune response. A critical component of these signaling pathways is the homotypic interaction of receptor and adapter proteins via specific protein interaction domains. Within the innate immune signaling cascade, homotypic interactions between members of the death domain family and the Toll/interleukin-1 receptor domain are particularly important. Here we discuss the current understanding of the molecular basis of these homotypic receptor:adapter interactions and their role in innate immune signal transduction.
Monie
Tom P
TP
Department of Biochemistry, University of Cambridge, Cambridge, UK.
Moncrieffe
Martin C
MC
Gay
Nicholas J
NJ
D000494:Allosteric Regulation / Q000276:immunology; D000818:Animals; D053468:CARD Signaling Adaptor Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D053418:Death Domain Receptor Signaling Adaptor Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D015801:Helminth Proteins / Q000276:immunology* / Q000378:metabolism; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D007239:Infections / Q000276:immunology; D054730:Protein Interaction Domains and Motifs; D011499:Protein Processing, Post-Translational / Q000276:immunology; D021381:Protein Transport / Q000276:immunology; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D013329:Structure-Activity Relationship; D051193:Toll-Like Receptors / Q000737:chemistry / Q000276:immunology
D053468:CARD Signaling Adaptor Proteins; D053418:Death Domain Receptor Signaling Adaptor Proteins; C435884:ES-62 protein, Acanthocheilonema viteae; D015801:Helminth Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D051193:Toll-Like Receptors