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| Title | The structures of the peptide transporters SLC15A3 and SLC15A4 reveal the recognition mechanisms for substrate and TASL. |
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| Journal, issue, pages | Structure, Vol. 33, Issue 2, Page 330-337.e4, Year 2025 |
| Publish date | Feb 6, 2025 |
Authors | Zhikuan Zhang / Shota Kasai / Kentaro Sakaniwa / Akiko Fujimura / Umeharu Ohto / Toshiyuki Shimizu / ![]() |
| PubMed Abstract | The solute carrier family 15 members 3 and 4 (SLC15A3 and SLC15A4) are closely related endolysosomal peptide transporters that transport free histidine and certain dipeptides from the lumen to ...The solute carrier family 15 members 3 and 4 (SLC15A3 and SLC15A4) are closely related endolysosomal peptide transporters that transport free histidine and certain dipeptides from the lumen to cytosol. Besides, SLC15A4 also functions as a scaffold protein for the recruitment of the adapter TASL for interferon regulatory factor 5 (IRF5) activation downstream of innate immune TLR7-9 signaling. However, the molecular basis for the substrate recognition and TASL recruitment by these membrane proteins is not well understood. Here, we report the cryoelectron microscopy (cryo-EM) structure of apo SLC15A3 and structures of SLC15A4 in the absence or presence of the substrate, revealing the specific dipeptide recognition mechanism. Each SLC15A3 and SLC15A4 protomer adopts an outward-facing conformation. Furthermore, we also present the cryo-EM structure of a SLC15A4-TASL complex. The N terminal region of TASL forms a helical structure that inserts deeply into the inward-facing cavity of SLC15A4. |
External links | Structure / PubMed:39719710 |
| Methods | EM (single particle) |
| Resolution | 2.83 - 3.91 Å |
| Structure data | EMDB-37897, PDB-8wx1: EMDB-37898, PDB-8wx2: EMDB-37899, PDB-8wx3: EMDB-37900, PDB-8wx4: EMDB-37901, PDB-8wx5: |
| Chemicals | ![]() ChemComp-LYS: ![]() ChemComp-LEU: |
| Source |
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Keywords | MEMBRANE PROTEIN / Transporter / Immune system |
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