Fig. 5: Proposed mechanism of SLC15A4−TASL signaling.
From: Structural basis for recruitment of TASL by SLC15A4 in human endolysosomal TLR signaling
Schematic model of the TASL- and SLC15A4-dependent IRF5 activation in endolysosomal TLR signaling. Apo SLC15A4 is located on the lysosomal lumen and adopts an outward-facing conformation. During the recruitment of TASL, SLC15A4 undergoes an outward-facing to an inward-facing conformational change, leading to the opening of the TASL-binding pocket and the subsequent binding to TASL from the cytosolic side. Activation of TLR7–9 triggers the phosphorylation of the SLC15A4-TASL module, resulting in the following recruitment and activation of transcription factor IRF5. The phosphorylated IRF5 dimer then enters the nucleus to regulate the production of inflammatory cytokines. SLC15A4 can be locked in the outward-facing conformation by a selective inhibitor, which blocks the SLC15A4-TASL interaction, thus interrupting the endolysosomal TLR signaling pathway. The red and blue dashed boxes indicate the activation and inhibition process of SLC15A4, respectively.
