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-Structure paper
タイトル | Extracellular domain of PepT1 interacts with TM1 to facilitate substrate transport. |
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ジャーナル・号・ページ | Structure, Vol. 30, Issue 7, Page 1035-11041.e3, Year 2022 |
掲載日 | 2022年7月7日 |
![]() | Jiemin Shen / Miaohui Hu / Xiao Fan / Zhenning Ren / Corinne Portioli / Xiuwen Yan / Mingqiang Rong / Ming Zhou / ![]() |
PubMed 要旨 | 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 ...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. |
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手法 | EM (単粒子) |
解像度 | 3.7 Å |
構造データ | EMDB-24922, PDB-7s8u: |
由来 |
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![]() | TRANSPORT PROTEIN / PepT1 / SLC15 / ECD / transporter / nanodisc |