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Sequence-structure-function relations of the mosquito leucine-rich repeat immune proteins.

Waterhouse RM, Povelones M, Christophides GK - BMC Genomics (2010)

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Genetic Medicine and Development, University of Geneva Medical School, 1 rue Michel-Servet, 1211 Geneva, Switzerland. robert.waterhouse@unige.ch

ABSTRACT

Background: 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. 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.

Results: The 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.

Conclusions: The 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.

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Orthologous genomic clusters of mosquito Short LRIM genes. Anopheles gambiae (red) chromosome (Chr), and orthologous Culex quinquefasciatus (purple) and Aedes aegypti (yellow) supercontigs (Scont) are depicted with LRIM genes (green), a guanine nucleotide exchange factor (GNEF) containing gene (blue), and repeat regions (light shading). Comparative sequence analyses reveal duplications (dashed lines) of LRIM8 in An. gambiae and of LRIM10 in Ae. aegypti, while LRIM7 and LRIM9 remain as single-copy orthologues. Some shuffling of LRIM gene orders and orientations has occurred, and the accumulation of repetitive elements has left the Ae. aegypti region ~4-fold larger.
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Figure 2: Orthologous genomic clusters of mosquito Short LRIM genes. Anopheles gambiae (red) chromosome (Chr), and orthologous Culex quinquefasciatus (purple) and Aedes aegypti (yellow) supercontigs (Scont) are depicted with LRIM genes (green), a guanine nucleotide exchange factor (GNEF) containing gene (blue), and repeat regions (light shading). Comparative sequence analyses reveal duplications (dashed lines) of LRIM8 in An. gambiae and of LRIM10 in Ae. aegypti, while LRIM7 and LRIM9 remain as single-copy orthologues. Some shuffling of LRIM gene orders and orientations has occurred, and the accumulation of repetitive elements has left the Ae. aegypti region ~4-fold larger.

Mentions: Comparative sequence analyses of the mosquito LRIM-like genes identified likely orthologous and paralogous relations. This was assisted by examination of orthologous genomic regions (synteny) among the three mosquitoes, which identified clusters of LRIM orthologues with local gene duplication and shuffling events. A cluster of short LRIMs (LRIMs 7, 8, 9, and 10) is in close proximity to a guanine nucleotide exchange factor (GNEF) containing gene found in all three species (Figure 2). Duplications of LRIM8 in An. gambiae and LRIM10 in Ae. aegypti have created two paralogous pairs, while LRIM7 and LRIM9 have remained as single-copy orthologues. The relative location and orientation of LRIM9 has remained conserved while LRIM10 appears inverted in An. gambiae. The LRIM7-LRIM8 pair has preserved its head-to-tail orientation in all three species (with the LRIM8B paralogue in An. gambiae), but in Ae. aegypti it has relocated relative to the duplicated LRIM10. The genomic span of the orthologous region in Ae. aegypti is about four times greater, primarily due to the accumulation of numerous repetitive elements and consistent with the overall ~4.6-fold larger span of synteny regions in Ae. aegypti compared to An. gambiae [20]. This notable genomic expansion in Ae. aegypti is also observed in the AgAPL1 cluster, which is located with LRIM 3, 4, and 11 orthologues between conserved BRACA2-like (breast cancer susceptibility protein) and Zinc finger genes. Examining the genomic organisation of LRIM-like genes thus reveals events of gene duplication and shuffling that have shaped the evolution of the LRIM gene family in mosquitoes.


Sequence-structure-function relations of the mosquito leucine-rich repeat immune proteins.

Waterhouse RM, Povelones M, Christophides GK - BMC Genomics (2010)

Orthologous genomic clusters of mosquito Short LRIM genes. Anopheles gambiae (red) chromosome (Chr), and orthologous Culex quinquefasciatus (purple) and Aedes aegypti (yellow) supercontigs (Scont) are depicted with LRIM genes (green), a guanine nucleotide exchange factor (GNEF) containing gene (blue), and repeat regions (light shading). Comparative sequence analyses reveal duplications (dashed lines) of LRIM8 in An. gambiae and of LRIM10 in Ae. aegypti, while LRIM7 and LRIM9 remain as single-copy orthologues. Some shuffling of LRIM gene orders and orientations has occurred, and the accumulation of repetitive elements has left the Ae. aegypti region ~4-fold larger.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3020904&req=5

Figure 2: Orthologous genomic clusters of mosquito Short LRIM genes. Anopheles gambiae (red) chromosome (Chr), and orthologous Culex quinquefasciatus (purple) and Aedes aegypti (yellow) supercontigs (Scont) are depicted with LRIM genes (green), a guanine nucleotide exchange factor (GNEF) containing gene (blue), and repeat regions (light shading). Comparative sequence analyses reveal duplications (dashed lines) of LRIM8 in An. gambiae and of LRIM10 in Ae. aegypti, while LRIM7 and LRIM9 remain as single-copy orthologues. Some shuffling of LRIM gene orders and orientations has occurred, and the accumulation of repetitive elements has left the Ae. aegypti region ~4-fold larger.
Mentions: Comparative sequence analyses of the mosquito LRIM-like genes identified likely orthologous and paralogous relations. This was assisted by examination of orthologous genomic regions (synteny) among the three mosquitoes, which identified clusters of LRIM orthologues with local gene duplication and shuffling events. A cluster of short LRIMs (LRIMs 7, 8, 9, and 10) is in close proximity to a guanine nucleotide exchange factor (GNEF) containing gene found in all three species (Figure 2). Duplications of LRIM8 in An. gambiae and LRIM10 in Ae. aegypti have created two paralogous pairs, while LRIM7 and LRIM9 have remained as single-copy orthologues. The relative location and orientation of LRIM9 has remained conserved while LRIM10 appears inverted in An. gambiae. The LRIM7-LRIM8 pair has preserved its head-to-tail orientation in all three species (with the LRIM8B paralogue in An. gambiae), but in Ae. aegypti it has relocated relative to the duplicated LRIM10. The genomic span of the orthologous region in Ae. aegypti is about four times greater, primarily due to the accumulation of numerous repetitive elements and consistent with the overall ~4.6-fold larger span of synteny regions in Ae. aegypti compared to An. gambiae [20]. This notable genomic expansion in Ae. aegypti is also observed in the AgAPL1 cluster, which is located with LRIM 3, 4, and 11 orthologues between conserved BRACA2-like (breast cancer susceptibility protein) and Zinc finger genes. Examining the genomic organisation of LRIM-like genes thus reveals events of gene duplication and shuffling that have shaped the evolution of the LRIM gene family in mosquitoes.

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Genetic Medicine and Development, University of Geneva Medical School, 1 rue Michel-Servet, 1211 Geneva, Switzerland. robert.waterhouse@unige.ch

ABSTRACT

Background: 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. 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.

Results: The 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.

Conclusions: The 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.

Show MeSH
Related in: MedlinePlus