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-Structure paper
タイトル | Structure and dynamics of Toll immunoreceptor activation in the mosquito Aedes aegypti. |
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ジャーナル・号・ページ | Nat Commun, Vol. 13, Issue 1, Page 5110, Year 2022 |
掲載日 | 2022年8月30日 |
著者 | Yoann Saucereau / Thomas H Wilson / Matthew C K Tang / Martin C Moncrieffe / Steven W Hardwick / Dimitri Y Chirgadze / Sandro G Soares / Maria Jose Marcaida / Nicholas J Gay / Monique Gangloff / |
PubMed 要旨 | Aedes aegypti has evolved to become an efficient vector for arboviruses but the mechanisms of host-pathogen tolerance are unknown. Immunoreceptor Toll and its ligand Spaetzle have undergone ...Aedes aegypti has evolved to become an efficient vector for arboviruses but the mechanisms of host-pathogen tolerance are unknown. Immunoreceptor Toll and its ligand Spaetzle have undergone duplication which may allow neofunctionalization and adaptation. Here we present cryo-EM structures and biophysical characterisation of low affinity Toll5A complexes that display transient but specific interactions with Spaetzle1C, forming asymmetric complexes, with only one ligand clearly resolved. Loop structures of Spaetzle1C and Toll5A intercalate, temporarily bridging the receptor C-termini to promote signalling. By contrast unbound receptors form head-to-head homodimers that keep the juxtamembrane regions far apart in an inactive conformation. Interestingly the transcriptional signature of Spaetzle1C differs from other Spaetzle cytokines and controls genes involved in innate immunity, metabolism and tissue regeneration. Taken together our results explain how upregulation of Spaetzle1C in the midgut and Toll5A in the salivary gland shape the concomitant immune response. |
リンク | Nat Commun / PubMed:36042238 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.41 - 4.23 Å |
構造データ | EMDB-11982, PDB-7b1b: EMDB-11983, PDB-7b1c: EMDB-11984, PDB-7b1d: |
化合物 | ChemComp-NAG: |
由来 |
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キーワード | IMMUNE SYSTEM / Mosquito vector biology / Toll receptor / LRR / Cystine knot domain |