Solute carrier family 15 member 4 protein (SLC15A4, also kno...

created [InstanceEdit:9861010] Shamovsky, Veronica, 2024-02-13
dbId 9861009
displayName Solute carrier family 15 member 4 protein (SLC15A4, also kno...
literatureReference
modified [InstanceEdit:9910879] Shamovsky, Veronica, 2024-05-22
schemaClass Summation
text Solute carrier family 15 member 4 protein (SLC15A4, also known as PHT1) and TLR adaptor interacting with SLC15A4 on the lysosome (TASL) control the activation of the key transcription factor IRF5 in response to activation of endosomal Toll-like receptors (TLR7, TLR8, and TLR9) (Heinz L et al., 2020; Zhang H et al., 2023). TASL is recruited to SLC15A4, located on the endolysosomal membrane (Heinz L et al., 2020; Zhang H et al., 2023; Chen X et al., 2023; Boeszoermeny A et al., 2023). Structural studies using cryo-electron microscopy (cryo-EM) reveal that formation of the human SLC15A4:TASL complex involves transition of SLC15A4 from the endolysosomal lumen-exposed outward-facing apo state to an inward-facing state in which the negatively-charged binding pocket of SLC15A4 facilitates the insertion of the N-terminal helix of TASL (Chen X et al., 2023; Boeszoermeny A et al., 2023). Mutagenesis analysis further confirms that the N-terminus of TASL interacts with SLC15A4 (Heinz L et al., 2020; Zhang H et al., 2023; Boeszoermeny A et al., 2023; Chen X et al., 2023). Similar findings have been reported for chicken SLC15A4 and TASL (Custodio TF et al., 2023). The formation of SLC15A4:TASL complex is required for endosomal TLR-induced IRF5 activation, and subsequent translocation of activated IRF5 to the nucleus (Heinz L et al., 2020; Zhang H et al., 2023; Chen X et al., 2023; Boeszoermeny A et al., 2023). Disruption of the SLC15A4:TASL complex abolishes TLR-induced IRF5 activation (Heinz L. et al., 2020; Zhang H et al., 2023; Chen X et al., 2023; Boeszoermeny A et al., 2023).
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