7NQK

Cryo-EM structure of the mammalian peptide transporter PepT2

Summary for 7NQK

• Entry DOI: 10.2210/pdb7nqk/pdb
• EMDB information: 12528
• Descriptor: Solute carrier family 15 member 2, nanobody (2 entities in total)
• Functional Keywords: proton-coupled peptide transporter, membrane protein
• Biological source: Rattus norvegicus (Rat); More
• Total number of polymer chains: 2
• Total formula weight: 96971.95

Authors

Parker, J.L.,Deme, J.C.,Lea, S.M.,Newstead, S. (deposition date: 2021-03-01, release date: 2021-07-07, Last modification date: 2025-07-02)

Primary citation

Parker, J.L.,Deme, J.C.,Wu, Z.,Kuteyi, G.,Huo, J.,Owens, R.J.,Biggin, P.C.,Lea, S.M.,Newstead, S.
Cryo-EM structure of PepT2 reveals structural basis for proton-coupled peptide and prodrug transport in mammals.
Sci Adv, 7:-, 2021

PubMed Abstract: The SLC15 family of proton-coupled solute carriers PepT1 and PepT2 play a central role in human physiology as the principal route for acquiring and retaining dietary nitrogen. A remarkable feature of the SLC15 family is their extreme substrate promiscuity, which has enabled the targeting of these transporters for the improvement of oral bioavailability for several prodrug molecules. Although recent structural and biochemical studies on bacterial homologs have identified conserved sites of proton and peptide binding, the mechanism of peptide capture and ligand promiscuity remains unclear for mammalian family members. Here, we present the cryo-electron microscopy structure of the outward open conformation of the rat peptide transporter PepT2 in complex with an inhibitory nanobody. Our structure, combined with molecular dynamics simulations and biochemical and cell-based assays, establishes a framework for understanding peptide and prodrug recognition within this pharmaceutically important transporter family.

PubMed: 34433568
DOI: 10.1126/sciadv.abh3355

Experimental method

ELECTRON MICROSCOPY (3.5 Å)