7S8U

Cryo-EM structure of a mammalian peptide transporter (PepT1/slc15a1) in nanodisc

Summary for 7S8U

• Entry DOI: 10.2210/pdb7s8u/pdb
• EMDB information: 24922
• Descriptor: Solute carrier family 15 member 1 (1 entity in total)
• Functional Keywords: pept1, slc15, ecd, transporter, nanodisc, transport protein
• Biological source: Equus caballus (horse)
• Total number of polymer chains: 1
• Total formula weight: 78723.99

Authors

Shen, J.,Zhou, M. (deposition date: 2021-09-19, release date: 2022-07-20, Last modification date: 2025-06-04)

Primary citation

Shen, J.,Hu, M.,Fan, X.,Ren, Z.,Portioli, C.,Yan, X.,Rong, M.,Zhou, M.
Extracellular domain of PepT1 interacts with TM1 to facilitate substrate transport.
Structure, 30:1035-1041.e3, 2022

PubMed Abstract: Mammalian peptide transporters, PepT1 and PepT2, mediate uptake of small peptides and are essential for their absorption. PepT also mediates absorption of many drugs and prodrugs to enhance their bioavailability. PepT has twelve transmembrane (TM) helices that fold into an N-terminal domain (NTD, TM1-6) and a C-terminal domain (CTD, TM7-12) and has a large extracellular domain (ECD) between TM9-10. It is well recognized that peptide transport requires movements of the NTD and CTD, but the role of the ECD in PepT1 remains unclear. Here we report the structure of horse PepT1 encircled in lipid nanodiscs and captured in the inward-open apo conformation. The structure shows that the ECD bridges the NTD and CTD by interacting with TM1. Deletion of ECD or mutations to the ECD-TM1 interface impairs the transport activity. These results demonstrate an important role of ECD in PepT1 and enhance our understanding of the transport mechanism in PepT1.

PubMed: 35580608
DOI: 10.1016/j.str.2022.04.011

Experimental method

ELECTRON MICROSCOPY (3.7 Å)