Evidence map›Paper›PMID 34433568›Full record

ArticleScience advances2021

Cryo-EM structure of PepT2 reveals structural basis for proton-coupled peptide and prodrug transport in mammals.

Joanne L Parker, Justin C Deme, Zhiyi Wu, Gabriel Kuteyi, Jiandong Huo, Raymond J Owens, Philip C Biggin, Susan M Lea, Simon Newstead

Open access · goldAbstract read
In one paragraph

Article in Science advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
5.0field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

34 citing papers in PubMed, 70 citations in OpenAlex.

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  15. Structure of the human heparan-α-glucosaminidebioRxiv : the preprint server for biology · 2024
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 2 countries.

Joanne L ParkerDepartment of Biochemistry, University of Oxford, Oxford OX1 3QU, UK. simon.newstead@bioch.ox.ac.uk joanne.parker@bioch.ox.ac.uk susan.lea@path.ox.ac.uk philip.biggin@bioch.ox.ac.uk.ORCID 0000-0003-2964-2720
Justin C DemeDunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK.ORCID 0000-0001-8811-9871
Zhiyi WuDepartment of Biochemistry, University of Oxford, Oxford OX1 3QU, UK.ORCID 0000-0002-7615-7851
Gabriel KuteyiDepartment of Biochemistry, University of Oxford, Oxford OX1 3QU, UK.
Jiandong HuoStructural Biology, The Rosalind Franklin Institute, Harwell Science and Innovation Campus, Didcot, UK.ORCID 0000-0002-7899-1815
Raymond J OwensStructural Biology, The Rosalind Franklin Institute, Harwell Science and Innovation Campus, Didcot, UK.ORCID 0000-0002-3705-2993
Philip C BigginDepartment of Biochemistry, University of Oxford, Oxford OX1 3QU, UK. simon.newstead@bioch.ox.ac.uk joanne.parker@bioch.ox.ac.uk susan.lea@path.ox.ac.uk philip.biggin@bioch.ox.ac.uk.ORCID 0000-0001-5100-8836
Susan M LeaDunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK. simon.newstead@bioch.ox.ac.uk joanne.parker@bioch.ox.ac.uk susan.lea@path.ox.ac.uk philip.biggin@bioch.ox.ac.uk.ORCID 0000-0001-9287-8053
Simon NewsteadDepartment of Biochemistry, University of Oxford, Oxford OX1 3QU, UK. simon.newstead@bioch.ox.ac.uk joanne.parker@bioch.ox.ac.uk susan.lea@path.ox.ac.uk philip.biggin@bioch.ox.ac.uk.ORCID 0000-0001-7432-2270
University of Oxford · GBCentre for Human Genetics · GB

Funding

Biotechnology and Biological Sciences Research Council BB/L01386X/1Medical Research Council G0900399Wellcome Trust 209194/Z/17/Z
6 · The paper itself

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.

Indexed as

ProdrugsSymportersAnimalsCryoelectron MicroscopyMammalsMembrane Transport ProteinsPeptidesPeptide Transporter 1ProtonsRatsMembrane Transport ProteinsPeptidesPeptide Transporter 1ProdrugsProtonsSymporters

Identifiers

PMID34433568
PMCPMC8386928
OpenAlexW3194026436

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.