Figure 1. Membrane-bound pattern recognition receptors. Toll-like receptors (TLRs) normally exist as heterodimers, each polypeptide consisting of an extracellular ligand-sensing leucine rich repeat (LRR) domain and an intracellular signalling Toll/interleukin-1 receptor (TIR) domain. The C-type lectin receptors comprises a large family of proteins containing C-type lectin domains (CTLDs), and includes mannose receptor (MR), dendritic cell-specific ICAM-3 grabbing nonintegrin (DC-SIGN) and Dectin-1. MR is a type I transmembrane protein that consists of an N-terminal cysteine-rich (CR) domain followed by a fibronectin type II and eight CTLDs. DC-SIGN is a type II transmembrane protein that contains a single extracellular CTLD and forms tetramers in its native state. Dectin-1 consists of a single extracellular C-terminal CTLD and an intracellular immunoreceptor tyrosine-based activation motif (ITAM)-like motif. Scavenger receptor A (SR-A) and macrophage receptor with collagenous structure (MARCO) are both members of group A of the scavenger receptor family. SR-A is a trimeric type II transmembrane protein that contains a C-terminal scavenger receptor cysteine-rich (SRCR) domain, an -helical coiled-coil domain and a collagenous domain. MARCO has a very similar overall structure to SR-A, but lacks the coiled-coil domain and contains a much more extensive collagenous domain. Adapted by permission from Macmillan Publishers Ltd: Medzhitov R et al., A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature 388: 394–397, copyright 1997, http://www.nature.com and reprinted, with permission, from the Annual Review of Immunology, Volume 23 © 2005 by Annual Reviews, http://www.annualreviews.org.

Figure 2. Intracellular pattern recognition receptors. The NOD-like receptors (NLRs) sense the cytoplasmic environment and they are characterized by a conserved three-part structure. A series of leucine rich repeats (LRRs) forms the domain responsible for ligand recognition, resulting in self-association of activated receptors through the central NACT domain (domain present in NAIP, CIITA, HET-E and TP1; also called NBS, NOD). Signals are then relayed via the N-terminal effector domain that can be a caspase recruitment domain (CARD), a pyrin domain (PYD) or a baculovirus IAP (inhibitor of apoptosis protein) repeat (BIR) domain, binding to adaptor molecules containing identical domains. The NALP-family contains PYD effector domains and NALP1 additionally contains a CARD domain and a ‘function-to-find’ domain (FIIND) at its C-terminal end. The NOD-family contains N-terminal CARD domains, except for NOD5 that has an N-terminal domain with only very weak sequence similarity with known CARD domains. The three remaining members of the family are the CARD-containing class II trans-activator (CIITA), ICE-protease activating factor (IPAF) and BIR-containing neuronal apoptosis inhibitory protein (NAIP). The RIG-like helicases, RIG-I and MDA5, each contains two N-terminal CARD domains and a helicase domain. Adapted by permission from Macmillan Publishers Ltd. Meylan et al., 2006, http://www.nature.com.