7B1C

Cryo-EM of Aedes Aegypti Toll5A trimer bound to Spz1C

7B1C の概要

• エントリーDOI: 10.2210/pdb7b1c/pdb
• EMDBエントリー: 11982 11983 11984
• 分子名称: Toll-like receptor, AAEL013433-PA, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• 機能のキーワード: mosquito vector biology, toll receptor, lrr, cystine knot domain, immune system
• 由来する生物種: Aedes aegypti (yellow fever mosquito); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 296177.19

構造登録者

Gangloff, M.,Hardwick, S.W.,Chirgadze, D.Y. (登録日: 2020-11-24, 公開日: 2022-07-13, 最終更新日: 2024-11-13)

主引用文献

Saucereau, Y.,Wilson, T.H.,Tang, M.C.K.,Moncrieffe, M.C.,Hardwick, S.W.,Chirgadze, D.Y.,Soares, S.G.,Marcaida, M.J.,Gay, N.J.,Gangloff, M.
Structure and dynamics of Toll immunoreceptor activation in the mosquito Aedes aegypti.
Nat Commun, 13:5110-5110, 2022

PubMed Abstract: 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.

PubMed: 36042238
DOI: 10.1038/s41467-022-32690-6

実験手法

ELECTRON MICROSCOPY (3.74 Å)