8WX4

Cryo-EM structure of human SLC15A4 in complex with Lys-Leu (outward-facing open)

Summary for 8WX4

• Entry DOI: 10.2210/pdb8wx4/pdb
• EMDB information: 37900
• Descriptor: Solute carrier family 15 member 4, LYSINE, LEUCINE (3 entities in total)
• Functional Keywords: transporter, membrane protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 130269.09

Authors

Sakaniwa, K.,Zhang, Z.,Ohto, U.,Shimizu, T. (deposition date: 2023-10-27, release date: 2023-12-13, Last modification date: 2025-06-25)

Primary citation

Zhang, Z.,Kasai, S.,Sakaniwa, K.,Fujimura, A.,Ohto, U.,Shimizu, T.
The structures of the peptide transporters SLC15A3 and SLC15A4 reveal the recognition mechanisms for substrate and TASL.
Structure, 33:330-, 2025

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 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.

PubMed: 39719710
DOI: 10.1016/j.str.2024.11.019

Experimental method

ELECTRON MICROSCOPY (3.12 Å)