7NQK

Cryo-EM structure of the mammalian peptide transporter PepT2

7NQK の概要

• エントリーDOI: 10.2210/pdb7nqk/pdb
• EMDBエントリー: 12528
• 分子名称: Solute carrier family 15 member 2, nanobody (2 entities in total)
• 機能のキーワード: proton-coupled peptide transporter, membrane protein
• 由来する生物種: Rattus norvegicus (Rat); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 96971.95

構造登録者

Parker, J.L.,Deme, J.C.,Lea, S.M.,Newstead, S. (登録日: 2021-03-01, 公開日: 2021-07-07, 最終更新日: 2025-07-02)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (3.5 Å)