Department of Genetic Medicine and Development, University of Geneva Medical School, 1 rue Michel-Servet, 1211 Geneva, Switzerland.
BMC Genomics. 2010 Sep 30;11:531. doi: 10.1186/1471-2164-11-531.
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.
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.
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.
昆虫固有免疫反应相关因子的发现和特性研究推动了哺乳动物和其他生物免疫系统成分的阐明。以疟蚊，冈比亚按蚊的免疫系统反应为研究对象，揭示了一系列防御病原体感染的成分和机制。其中两个免疫因子是 LRIM1 和 APL1C，它们是富含亮氨酸重复（LRR）的蛋白，能激活对抗疟原虫的补体样防御反应。除了 LRR 结构域外，这些富含亮氨酸重复的免疫（LRIM）蛋白还具有几个结构特征，包括信号肽、半胱氨酸残基模式和卷曲螺旋结构域。
LRIM1 和 APL1C 相关基因的鉴定和特性研究揭示了潜在的新固有免疫因子，并进一步了解了它们的可能分子功能。利用 LRIM1 和 APL1C 的共享特征进行基因组扫描，在具有测序基因组的三种病媒蚊子（冈比亚按蚊、埃及伊蚊和库蚊）中，鉴定出 20 多个具有所有或大部分序列特征的 LRIM 样基因。比较序列分析表明，蚊子 LRIM 样基因家族的特征是 LRR 的数量不同，长度为 6 到 14 个。长 LRIM 亚家族有 10 个或更多的 LRR，短 LRIM 有 6 个或 7 个 LRR，也共享 LRIM1 和 APL1C 的信号肽、半胱氨酸残基模式和卷曲螺旋序列特征。“TM”LRIM 具有预测的 C 端跨膜区，而“无卷曲螺旋”LRIM 具有特征性的 LRIM 序列特征，但缺乏 C 端卷曲螺旋结构域。
LRIM LRR 结构域的进化可塑性可能为多样性的识别特性提供模板，而其卷曲螺旋结构域可能参与 LRIM 蛋白复合物的形成或介导与其他免疫蛋白的相互作用。保守的 LRIM 半胱氨酸残基模式可能对结构折叠稳定性和蛋白复合物的形成很重要。蚊子 LRIM 的这些序列-结构-功能关系将有助于指导其实验阐明其在蚊子免疫中的分子作用。
