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Structural snapshots of human PepT1 and PepT2 reveal mechanistic insights into substrate and drug transport across epithelial membranes

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Structural snapshots of human PepT1 and PepT2 reveal mechanistic insights into substrate and drug transport across epithelial membranes. / Killer, Maxime; Wald, Jiri; Pieprzyk, Joanna; Marlovits, Thomas C; Löw, Christian.

In: SCI ADV, Vol. 7, No. 45, eabk3259, 05.11.2021.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Killer, M, Wald, J, Pieprzyk, J, Marlovits, TC & Löw, C 2021, 'Structural snapshots of human PepT1 and PepT2 reveal mechanistic insights into substrate and drug transport across epithelial membranes', SCI ADV, vol. 7, no. 45, eabk3259. https://doi.org/10.1126/sciadv.abk3259

APA

Killer, M., Wald, J., Pieprzyk, J., Marlovits, T. C., & Löw, C. (2021). Structural snapshots of human PepT1 and PepT2 reveal mechanistic insights into substrate and drug transport across epithelial membranes. SCI ADV, 7(45), [eabk3259]. https://doi.org/10.1126/sciadv.abk3259

Vancouver

Killer M, Wald J, Pieprzyk J, Marlovits TC, Löw C. Structural snapshots of human PepT1 and PepT2 reveal mechanistic insights into substrate and drug transport across epithelial membranes. SCI ADV. 2021 Nov 5;7(45). eabk3259. https://doi.org/10.1126/sciadv.abk3259

Bibtex

@article{fa3732ba80a14671b0b0c63c7012b842,
title = "Structural snapshots of human PepT1 and PepT2 reveal mechanistic insights into substrate and drug transport across epithelial membranes",
abstract = "The uptake of peptides in mammals plays a crucial role in nutrition and inflammatory diseases. This process is mediated by promiscuous transporters of the solute carrier family 15, which form part of the major facilitator superfamily. Besides the uptake of short peptides, peptide transporter 1 (PepT1) is a highly abundant drug transporter in the intestine and represents a major route for oral drug delivery. PepT2 also allows renal drug reabsorption from ultrafiltration and brain-to-blood efflux of neurotoxic compounds. Here, we present cryogenic electron microscopy (cryo-EM) structures of human PepT1 and PepT2 captured in four different states throughout the transport cycle. The structures reveal the architecture of human peptide transporters and provide mechanistic insights into substrate recognition and conformational transitions during transport. This may support future drug design efforts to increase the bioavailability of different drugs in the human body.",
author = "Maxime Killer and Jiri Wald and Joanna Pieprzyk and Marlovits, {Thomas C} and Christian L{\"o}w",
year = "2021",
month = nov,
day = "5",
doi = "10.1126/sciadv.abk3259",
language = "English",
volume = "7",
journal = "SCI ADV",
issn = "2375-2548",
publisher = "American Association for the Advancement of Science",
number = "45",

}

RIS

TY - JOUR

T1 - Structural snapshots of human PepT1 and PepT2 reveal mechanistic insights into substrate and drug transport across epithelial membranes

AU - Killer, Maxime

AU - Wald, Jiri

AU - Pieprzyk, Joanna

AU - Marlovits, Thomas C

AU - Löw, Christian

PY - 2021/11/5

Y1 - 2021/11/5

N2 - The uptake of peptides in mammals plays a crucial role in nutrition and inflammatory diseases. This process is mediated by promiscuous transporters of the solute carrier family 15, which form part of the major facilitator superfamily. Besides the uptake of short peptides, peptide transporter 1 (PepT1) is a highly abundant drug transporter in the intestine and represents a major route for oral drug delivery. PepT2 also allows renal drug reabsorption from ultrafiltration and brain-to-blood efflux of neurotoxic compounds. Here, we present cryogenic electron microscopy (cryo-EM) structures of human PepT1 and PepT2 captured in four different states throughout the transport cycle. The structures reveal the architecture of human peptide transporters and provide mechanistic insights into substrate recognition and conformational transitions during transport. This may support future drug design efforts to increase the bioavailability of different drugs in the human body.

AB - The uptake of peptides in mammals plays a crucial role in nutrition and inflammatory diseases. This process is mediated by promiscuous transporters of the solute carrier family 15, which form part of the major facilitator superfamily. Besides the uptake of short peptides, peptide transporter 1 (PepT1) is a highly abundant drug transporter in the intestine and represents a major route for oral drug delivery. PepT2 also allows renal drug reabsorption from ultrafiltration and brain-to-blood efflux of neurotoxic compounds. Here, we present cryogenic electron microscopy (cryo-EM) structures of human PepT1 and PepT2 captured in four different states throughout the transport cycle. The structures reveal the architecture of human peptide transporters and provide mechanistic insights into substrate recognition and conformational transitions during transport. This may support future drug design efforts to increase the bioavailability of different drugs in the human body.

U2 - 10.1126/sciadv.abk3259

DO - 10.1126/sciadv.abk3259

M3 - SCORING: Journal article

C2 - 34730990

VL - 7

JO - SCI ADV

JF - SCI ADV

SN - 2375-2548

IS - 45

M1 - eabk3259

ER -