Urbach Jonathan M, Ausubel Frederick M
Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114.
Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114;
Proc Natl Acad Sci U S A. 2017 Jan 31;114(5):1063-1068. doi: 10.1073/pnas.1619730114. Epub 2017 Jan 17.
There are intriguing parallels between plants and animals, with respect to the structures of their innate immune receptors, that suggest universal principles of innate immunity. The cytosolic nucleotide binding site-leucine rich repeat (NBS-LRR) resistance proteins of plants (R-proteins) and the so-called NOD-like receptors of animals (NLRs) share a domain architecture that includes a STAND (signal transduction ATPases with numerous domains) family NTPase followed by a series of LRRs, suggesting inheritance from a common ancestor with that architecture. Focusing on the STAND NTPases of plant R-proteins, animal NLRs, and their homologs that represent the NB-ARC (nucleotide-binding adaptor shared by APAF-1, certain R gene products and CED-4) and NACHT (named for NAIP, CIIA, HET-E, and TEP1) subfamilies of the STAND NTPases, we analyzed the phylogenetic distribution of the NBS-LRR domain architecture, used maximum-likelihood methods to infer a phylogeny of the NTPase domains of R-proteins, and reconstructed the domain structure of the protein containing the common ancestor of the STAND NTPase domain of R-proteins and NLRs. Our analyses reject monophyly of plant R-proteins and NLRs and suggest that the protein containing the last common ancestor of the STAND NTPases of plant R-proteins and animal NLRs (and, by extension, all NB-ARC and NACHT domains) possessed a domain structure that included a STAND NTPase paired with a series of tetratricopeptide repeats. These analyses reject the hypothesis that the domain architecture of R-proteins and NLRs was inherited from a common ancestor and instead suggest the domain architecture evolved at least twice. It remains unclear whether the NBS-LRR architectures were innovations of plants and animals themselves or were acquired by one or both lineages through horizontal gene transfer.
植物和动物在其天然免疫受体结构方面存在有趣的相似之处，这表明了天然免疫的普遍原则。植物的胞质核苷酸结合位点富含亮氨酸重复序列（NBS-LRR）抗性蛋白（R蛋白）和动物的所谓NOD样受体（NLRs）具有共同的结构域架构，其中包括一个STAND（具有多个结构域的信号转导ATP酶）家族NTP酶，其后是一系列LRR，这表明它们继承自具有该架构的共同祖先。我们聚焦于植物R蛋白、动物NLRs及其同源物中的STAND NTP酶，它们分别代表STAND NTP酶的NB-ARC（由APAF-1、某些R基因产物和CED-4共享的核苷酸结合衔接子）和NACHT（以NAIP、CIIA、HET-E和TEP1命名）亚家族，分析了NBS-LRR结构域架构的系统发育分布，使用最大似然法推断R蛋白NTP酶结构域的系统发育，并重建了包含植物R蛋白和NLRs的STAND NTP酶结构域共同祖先的蛋白质的结构域结构。我们的分析否定了植物R蛋白和NLRs的单系性，并表明包含植物R蛋白和动物NLRs的STAND NTP酶最后共同祖先的蛋白质（进而包括所有NB-ARC和NACHT结构域）具有一种结构域结构，其中包括一个与一系列四肽重复序列配对的STAND NTP酶。这些分析否定了R蛋白和NLRs的结构域架构继承自共同祖先的假说，反而表明该结构域架构至少进化了两次。目前尚不清楚NBS-LRR架构是植物和动物自身的创新，还是一个或两个谱系通过水平基因转移获得的。
