8JZU

SLC15A4_TASL complex

8JZU の概要

• エントリーDOI: 10.2210/pdb8jzu/pdb
• EMDBエントリー: 36753
• 分子名称: SLC15A4-TSLAA/EGPF tag protein, TLR adapter-Green fluorescent protein, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• 機能のキーワード: endolysosomal transporter, protein transport
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 95744.87

構造登録者

Zhang, S.S.,Chen, X.D.,Xie, M. (登録日: 2023-07-06, 公開日: 2023-09-27, 最終更新日: 2025-05-28)

主引用文献

Chen, X.,Xie, M.,Zhang, S.,Monguio-Tortajada, M.,Yin, J.,Liu, C.,Zhang, Y.,Delacretaz, M.,Song, M.,Wang, Y.,Dong, L.,Ding, Q.,Zhou, B.,Tian, X.,Deng, H.,Xu, L.,Liu, X.,Yang, Z.,Chang, Q.,Na, J.,Zeng, W.,Superti-Furga, G.,Rebsamen, M.,Yang, M.
Structural basis for recruitment of TASL by SLC15A4 in human endolysosomal TLR signaling.
Nat Commun, 14:6627-6627, 2023

PubMed Abstract: Toll-like receptors (TLRs) are a class of proteins that play critical roles in recognizing pathogens and initiating innate immune responses. TASL, a recently identified innate immune adaptor protein for endolysosomal TLR7/8/9 signaling, is recruited by the lysosomal proton-coupled amino-acid transporter SLC15A4, and then activates IRF5, which in turn triggers the transcription of type I interferons and cytokines. Here, we report three cryo-electron microscopy (cryo-EM) structures of human SLC15A4 in the apo monomeric and dimeric state and as a TASL-bound complex. The apo forms are in an outward-facing conformation, with the dimeric form showing an extensive interface involving four cholesterol molecules. The structure of the TASL-bound complex reveals an unprecedented interaction mode with solute carriers. During the recruitment of TASL, SLC15A4 undergoes a conformational change from an outward-facing, lysosomal lumen-exposed state to an inward-facing state to form a binding pocket, allowing the N-terminal helix of TASL to be inserted into. Our findings provide insights into the molecular basis of regulatory switch involving a human solute carrier and offers an important framework for structure-guided drug discovery targeting SLC15A4-TASL-related human autoimmune diseases.

PubMed: 37863913
DOI: 10.1038/s41467-023-42210-9

実験手法

ELECTRON MICROSCOPY (3.05 Å)