Abstract
BackgroundThe discovery and characterisation of factors governing innate immune responses in insects has driven the elucidation of many immune system components in mammals and other organisms. Focusing on the immune system responses of the malaria mosquito, Anopheles gambiae, has uncovered an array of components and mechanisms involved in defence against pathogen infections. Two of these immune factors are LRIM1 and APL1C, which are leucine-rich repeat (LRR) containing proteins that activate complement-like defence responses against malaria parasites. In addition to their LRR domains, these leucine-rich repeat immune (LRIM) proteins share several structural features including signal peptides, patterns of cysteine residues, and coiled-coil domains.ResultsThe identification and characterisation of genes related to LRIM1 and APL1C revealed putatively novel innate immune factors and furthered the understanding of their likely molecular functions. Genomic scans using the shared features of LRIM1 and APL1C identified more than 20 LRIM-like genes exhibiting all or most of their sequence features in each of three disease-vector mosquitoes with sequenced genomes: An. gambiae, Aedes aegypti, and Culex quinquefasciatus. Comparative sequence analyses revealed that this family of mosquito LRIM-like genes is characterised by a variable number of 6 to 14 LRRs of different lengths. The "Long" LRIM subfamily, with 10 or more LRRs, and the "Short" LRIMs, with 6 or 7 LRRs, also share the signal peptide, cysteine residue patterning, and coiled-coil sequence features of LRIM1 and APL1C. The "TM" LRIMs have a predicted C-terminal transmembrane region, and the "Coil-less" LRIMs exhibit the characteristic LRIM sequence signatures but lack the C-terminal coiled-coil domains.ConclusionsThe evolutionary plasticity of the LRIM LRR domains may provide templates for diverse recognition properties, while their coiled-coil domains could be involved in the formation of LRIM protein complexes or mediate interactions with other immune proteins. The conserved LRIM cysteine residue patterns are likely to be important for structural fold stability and the formation of protein complexes. These sequence-structure-function relations of mosquito LRIMs will serve to guide the experimental elucidation of their molecular roles in mosquito immunity.
Highlights
The discovery and characterisation of factors governing innate immune responses in insects has driven the elucidation of many immune system components in mammals and other organisms
The search for leucine-rich repeat (LRR)-containing genes with sequence features most closely resembling AgLRIM1 and AgAPL1C employed a combination of approaches and identified 24 An. gambiae, Ae. aegypti, and Cx. quinquefasciatus leucine-rich repeat immune (LRIM)-like genes
The mosquito LRIMs with all the key sequence features can be grouped into the “Long” subfamily with 10 or more LRRs that includes AgLRIM1 and AgAPL1C, and the “Short” LRIMs with only 6 or 7 LRRs (Figure 1)
Summary
The discovery and characterisation of factors governing innate immune responses in insects has driven the elucidation of many immune system components in mammals and other organisms. Focusing on the immune system responses of the malaria mosquito, Anopheles gambiae, has uncovered an array of components and mechanisms involved in defence against pathogen infections Two of these immune factors are LRIM1 and APL1C, which are leucine-rich repeat (LRR) containing proteins that activate complement-like defence responses against malaria parasites. Recent genetic and biochemical studies of immune system responses to malaria parasite infections in An. gambiae have linked three major antiparasitic factors together in a complement-like pathway that mediates parasite killing [2,3] Two of these factors, LRIM1 and APL1C, are leucine-rich repeat (LRR) containing proteins that form a disulphide-bridged complex that interacts with the third factor, thioester-containing protein 1 (TEP1) a complement C3-like protein. Laboratory testing of APL1 produced similar effects to LRIM1 silencing, with significantly increased numbers of developing P. berghei oocysts
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