8CNI

PHT1 in the outward facing conformation, bound to Sb27

Summary for 8CNI

• Entry DOI: 10.2210/pdb8cni/pdb
• EMDB information: 16758
• Descriptor: Solute carrier family 15 member 4, Sybody 27 (2 entities in total)
• Functional Keywords: pht1, peptide transporter, histidine transporter, sybody 27, sle, slc15a4, membrane protein
• Biological source: Gallus gallus (chicken); More
• Total number of polymer chains: 3
• Total formula weight: 90575.00

Authors

Custodio, T.,Killer, M.,Loew, C. (deposition date: 2023-02-23, release date: 2023-09-27, Last modification date: 2024-02-28)

Primary citation

Custodio, T.F.,Killer, M.,Yu, D.,Puente, V.,Teufel, D.P.,Pautsch, A.,Schnapp, G.,Grundl, M.,Kosinski, J.,Low, C.
Molecular basis of TASL recruitment by the peptide/histidine transporter 1, PHT1.
Nat Commun, 14:5696-5696, 2023

PubMed Abstract: PHT1 is a histidine /oligopeptide transporter with an essential role in Toll-like receptor innate immune responses. It can act as a receptor by recruiting the adaptor protein TASL which leads to type I interferon production via IRF5. Persistent stimulation of this signalling pathway is known to be involved in the pathogenesis of systemic lupus erythematosus (SLE). Understanding how PHT1 recruits TASL at the molecular level, is therefore clinically important for the development of therapeutics against SLE and other autoimmune diseases. Here we present the Cryo-EM structure of PHT1 stabilized in the outward-open conformation. By combining biochemical and structural modeling techniques we propose a model of the PHT1-TASL complex, in which the first 16 N-terminal TASL residues fold into a helical structure that bind in the central cavity of the inward-open conformation of PHT1. This work provides critical insights into the molecular basis of PHT1/TASL mediated type I interferon production.

PubMed: 37709742
DOI: 10.1038/s41467-023-41420-5

Experimental method

ELECTRON MICROSCOPY (3.35 Å)